It therefore contains three methoxyl gro_Poisons, Their Effects and Detection A Manual for the Use of Analytical Chemists and Experts

Narceine forms good crystals, the form being that of long,

four-sided rhombic prisms or fine bushy united needles.

Narceine hydrochloride crystallises with 5½H₂O and with 3H₂O; the

anhydrous salt melts at 190°-192°. The platinochloride is a definite

salt, m.p. 190°-191°; it decomposes at 195°-196°. The nitrate forms

good crystals, which decompose at 97°. Narceine also forms

crystalline salts with potassium and sodium; these may be obtained

by heating the base at 60°-70° with a 33 per cent. of NaHO or KHO.

The potassium compound melts at 90°, the sodium at 159°-160°. The

alkaloid is regenerated when the alkali salts are treated with acids

or with CO₂. Crude narceine may be purified by means of the sodium

salt; the latter is dissolved in alcohol and precipitated with

ether.

It is soluble in alcohol, but almost insoluble in alcohol and ether,

or benzene and ether; it is slightly soluble in ether, carbon

disulphide, and chloroform. It has no reaction on moist litmus

paper.

Benzole and petroleum ether extract narceine neither from acid nor

alkaline solutions; chloroform extracts narceine both from acid and

from alkaline solutions, the latter in small proportion only.

Narceine turns the plane of polarisation to the left, [α]_r_ =

66·7°. Narceine may be separated from narcotine by the addition of

ammonia to the acid aqueous solution; narcotine is fully

precipitated by ammonia, but narceine is left in solution.

In the subliming cell it melts at 134°, but gives no crystalline

sublimate. The tube melting-point of the trihydrate is 170°. The

melted substance is at first colourless; but on raising the

temperature, the usual transitions of colour through different

shades of brown to black are observed. If melted, and kept a few

degrees above its melting-point, and then cooled slowly, the residue

is straw-coloured, divided into lobes, most of which contain

feathery crystals.

At high temperatures narceine develops a herring-like odour; the

residue becomes darkish blue with iron chloride. Concentrated nitric

acid dissolves it with a yellow colour; on heating, red vapours are

produced; the fluid contains crystals of oxalic acid, and develops

with potash a volatile base. Concentrated sulphuric acid colours

pure narceine brown; but if impure, a blood-red or blue colour may

be produced. It does not reduce iron salts.

Fröhde’s reagent colours it first brown-green, then red, passing

into blue. Narceine forms precipitates with bichromate of potash,

chloride of gold, bichloride of platinum, and several other

reagents. The one formed by the addition of potassio zinc iodide is

in hair-like crystals, which after twenty-four hours become blue.

Weak iodine solution colours narceine crystals a black-blue; they

dissolve in water at 100° without colour, but on cooling again

separate with a violet or blue colour. If on a saturated solution of

narceine a particle of iodine is strewn, fine needle-like grey

crystals form around the iodine. A drop of “Nessler” solution, added

to solid narceine, at once strikes a brown colour; on diluting the

drop with a little water, beautiful little bundles of crystals

appear.--_Flückiger._

The following group reagents precipitate narceine:--picric acid,

tannin solution, and potassium dichromate on long standing. The

following give no precipitate:--mercuric cyanide, mercuric potas.

iodide, mercuric chloride, mercuric bromide, and potas. ferrocyanide

solutions.

§ 371. =Effects.=--The physiological action of narceine has been

variously interpreted by different observers. Claude Bernard[408]

thought it the most somniferous of the opium alkaloids. He said that

“the narceinic sleep was characterised by a profound calm and

absence of the excitability of morphine, the animals narcotised by

narceine on awaking returning to their natural state without

enfeeblement of the hind limbs or other sequelæ.” It has been amply

confirmed that narceine possesses somniferous properties, but

certainly not to the extent that Bernard’s observations led

physiologists to expect. In large doses there is some irritation of

the stomach and intestines, and vomiting occurs, and even diarrhœa;

moderate doses induce constipation. The maximum medicinal dose may

be put at ·14 grm. (or 2·26 grains), and a probably dangerous dose

would be three times that quantity.[409]

[408] _Compt. Rend._, lix. p. 406, 1864.

[409] See J. Bouchardat, _La Narcéine_, Thèse, Paris, 1865; Harley, _The

Old Vegetable Neurotics_, Lond.; Ch. Liné, _Études sur la Narcéine et

son Emploi Thérapeutique_, Thèse, Paris, 1865; also, Husemann’s

_Planzenstoffe_, in which these and other researches are summarised.

§ 372. =Papaverine= (C₂₁H₂₁NO₄) crystallises from alcohol in white

needles or scales. It possesses scarcely any alkaline reaction, but

its salts have an acid reaction; it has but little effect on a ray

of polarised light. It is almost insoluble in water; it is easily

soluble in acetone, amyl alcohol, alcohol, and chloroform. One part

of the alkaloid is dissolved in 36·6 of benzene, and in 76 parts of

amyl alcohol. Petroleum ether dissolves it by the aid of heat, but

the alkaloid separates in crystals on cooling. Chloroform extracts

it from either acid or alkaline solutions. Papaverine gives no

crystalline sublimate. The melting-point of pure samples in a tube

is 147°, with scarcely any colour; it solidifies again to crystals

on cooling; in the subliming cell it melts at 130°, and decomposes

about 149°; the vapours are alkaline; the residue is amorphous,

light brown, and is not characteristic. Concentrated sulphuric acid

colours it a deep violet-blue, and dissolves it to a violet, slowly

fading. This solution, by permanganate of potash, is first green and

then grey. Fröhde’s reagent gives a beautiful violet colour, which

becomes blue, and vanishes after twenty-four hours. Diluted

solutions of salts of papaverine are not precipitated by

phosphomolybdic acid. It is precipitated by ammonia, by the caustic

and carbonated alkalies, by potassic-cadmic iodide, iodine in

hydriodic acid, and by alkaloidal reagents generally--save by the

important exception mentioned above. A solution in amyl alcohol is

also precipitated by bromine; the precipitate is crystalline. An

alcoholic solution of platinic chloride also separates papaverine

platin chloride in crystals. An alcoholic solution of iodine, added

to an alcoholic solution of papaverine, separates in a little time

crystals of the composition C₂₁H₂₁NO₄I₃. From the mother-liquor, by

concentration, can be obtained needles of another iodine

combination, C₂₁H₂₁NO₄I₅; the latter heated above 100° parts with

free iodine. These compounds with iodine are decomposed by ammonia

and potash, papaverine separating. The decomposition may be watched

under the microscope. Nitric acid precipitates from a solution of

the sulphate a white nitrate soluble in excess; the precipitate does

not appear at once, but forms in the course of an hour; it is at

first amorphous, but subsequently crystalline; this, with its

physical properties, is a great assistance to identification.

§ 373. =Effects.=--Claude Bernard ranked papaverine with the

convulsants; probably the papaverine he had was impure. In any case,

subsequent observations have shown that it is to be classed rather

with the hypnotic principles of opium. Leidesdorf[410] administered

it to the insane, and noted slowness of the pulse, muscular

weakness, and drowsiness to follow. The doses were given

subcutaneously (·42 grm. of the hydrochloride). Baxt,[411]

experimenting with the frog, found that a milligramme caused deep

sleep and slowing of the heart’s action. This action on the heart is

witnessed also on the recently-removed frog’s heart. Guinea-pigs,

and other small animals poisoned by strychnine or thebaine, and then

given papaverine, did not seem to be so soon affected with tetanus

as when no such remedy was administered. The fatal dose of

papaverine for a man is unknown. I should conjecture that the least

quantity that would cause dangerous symptoms would be 1 grm. (15·4

grains).

[410] _Ztschr. d. Wien. Aerzte_, pp. 13, 115, 1868.

[411] _Arch. Anat. Phys._, p. 70, 1869.

§ 374. =Thebaine=, C₁₇H₁₅NO(OCH₃)₂.--Opium seldom contains much more

than 1 per cent. of this alkaloid. It usually forms needles or short

crystals. It is alkaline, and by rubbing becomes negatively

electric. It is almost insoluble in water, aqueous ammonia, and

solutions of the alkalies. It requires 10 parts of cold alcohol for

solution, and dissolves readily in hot. Ether, hot or cold, is also

a good solvent. 100 parts of benzene are required for 5·27 parts of

thebaine, and 100 of amyl alcohol for 1·67 parts. Chloroform

dissolves thebaine with difficulty out of both acid and alkaline

solutions; petroleum ether extracts it from neither. Thebaine melts

in a tube at 193°, sublimes at 135°. The sublimate is in minute

crystals, similar to theine; at higher temperatures (160° to 200°)

needles, cubes, and prisms are obtained. The residue is fawn

coloured. Fröhde’s reagent (as well as concentrated sulphuric acid)

dissolves it, with the production of a blood-red colour, passing

gradually into yellow. The precipitate with picric acid is yellow

and amorphous; with tannic acid yellow; with gold chloride,

red-yellow; and with platinic chloride, citron-yellow, gradually

becoming crystalline. A concentrated alcoholic solution of thebaine,

just neutralised with HCl, deposits well-formed rhombic crystals of

the composition C₁₉H₂₁NO₃HCl + H₂O.

If 200 mgrms. of thebaine are heated to boiling with 1·4 c.c. of HCl

and 2·8 c.c. of water, and the solution diluted, after boiling, with

4 c.c. of water, crystals of thebaine hydrochloride form in the

yellow fluid in the course of a few hours.--_Flückiger._

§ 375. =Effects.=--There is no disagreement of opinion as to the

action of thebaine. By the united testimony of all who have

experimented with it, the alkaloid belongs to those poisons which

produce tetanus, and the symptoms can scarcely be differentiated

from strychnia. In Baxt’s experiments on frogs he showed that there

was some considerable difference in details in the general course of

the symptoms, according to the dose of the poison. A small dose

(such, for example, as ·75 mgrm.) injected into a frog

subcutaneously produces immediate excitement, the animal jumping

about, and this stage lasting for about a minute; it then becomes

quieter, and has from three to six minutes’ sleep; in a little time

this comatose state is followed by reflex tetanic spasms and then

spontaneous tetanic spasms. With three times the dose, the tetanic

convulsions commence early, and death takes place in from two to six

hours. Baxt[412] found 6 to 7 mgrms. kill rabbits with tetanic

convulsions in from fifteen to twenty-five minutes. Crum Brown and

Fraser also found that 12 mgrms. injected into rabbits were fatal;

it may then be presumed that the lethal dose for a rabbit is about 5

mgrms. per kilo. A frog’s heart under the action of thebaine, and

removed from the body, beats quicker and ceases earlier than one in

distilled water. Thebaine has been administered to the insane

subcutaneously in doses of from 12 to 40 mgrms., when a rise of

temperature and an increase in the respiratory movements and in the

circulation were noticed.[413]

[412] _Sitzungsber. d. Wien. Akadem._, lvi. pp. 2, 89, 1867; _Arch. f.

Anat. u. Physiol._, Hft. 1, p. 112, 1869.

[413] F. W. Müller, _Das Thebaine, eine Monographie_, Diss., Marburg

1868.

The fatal dose for a man is not known; ·5 grm., or about 8 grains,

would probably be a poisonous quantity.

§ 376. =Cryptopine= (C₂₁H₂₃NO₅) was discovered by T. & H. Smith in

1867.[414] It is only contained in very minute traces in

opium--something like ·003 per cent. It is a crystalline substance,

the crystals being colourless, six-sided prisms, without odour, but

with a bitter taste, causing an after-sensation like peppermint. The

crystals melt at 217°, and congeal in a crystalline form again at

171°; at high temperatures they are decomposed with evolution of

ammoniacal vapour. Cryptopine is insoluble, or almost so, in ether,

water, and oil of turpentine; it is soluble in acetone, benzene, and

chloroform; the latter is the best solvent, or hot alcohol; it is

insoluble in aqueous ammonia and in solutions of the caustic

alkaloids. Cryptopine is strongly basic, neutralising fully mineral

acids. Concentrated sulphuric acid colours cryptopine pure blue, the

tint gradually fading from absorption of water from the atmosphere.

On a crystal of potassic nitrate being added, the colour changes

into a permanent green. With ferric chloride cryptopine gives no

colour--thus distinguishing it from morphine. The physiological

properties of cryptopine have been investigated by Dr. Harley;[415]

it has a narcotic action, about double as strong as narceine, and

four times weaker than morphine. Munk and Sippell[416] found that it

gave rise in animals to paralysis of the limbs, and occasionally

asphyxic convulsions before death.

[414] _Pharm. Journ. Trans._ [2], viii. pp. 495 and 716.

[415] _The Old Vegetable Neurotics._

[416] Munk, _Versuche über die Wirkung des Cryptopins_, Berlin, 1873.

Sippell, _Beiträge zur Kentniss des Cryptopins_, Marburg, 1874.

§ 377. =Rhœadine= (C₂₁H₂₁NO₆).--Rhœadine was separated from _Papaver

rhœas_ by Hesse, and has also been found in _Papaver somniferum_ and

in opium. Rhœadine is in the form of small anhydrous tasteless

prisms, melting at 230° and partly subliming. In a vacuum

sublimation is almost complete, and at a much lower temperature. It

is a very insoluble substance, and is scarcely dissolved, when

crystalline, by water, alcohol, ether, chloroform, benzene, and

solutions of the fixed or volatile alkalies. When in an amorphous

state it is rather soluble in ether, and may be dissolved out of any

substance by treating with dilute acetic acid, and neutralising by

ammonia, and shaking up with ether before the precipitate becomes

crystalline. Rhœadine is easily recognised by its striking a red

colour with hydrochloric acid. Either spontaneously or on gentle

warming, the colour is produced--one part of rhœadine will colour in

this way 10,000 parts of acid water blue or purple-red, 200,000

rose-red, and 800,000 pale red. The reaction depends on a splitting

up of the rhœadine into a colourless substance, _rhœadin_, and a red

colouring-matter. Rhœadine is not poisonous.

§ 378. =Pseudomorphine= (C₁₇H₁₉NO₄).--Pseudomorphine was discovered

by Pelletier and Thiboumery in 1835. As precipitated by ammonia out

of the hot solution, pseudomorphine falls as a white crystalline

precipitate; but if the solution is cold, the precipitate is

gelatinous. It possesses no taste, and has no action on vegetable

colours. On heating, it decomposes and then melts. It dissolves

easily in caustic alkalies and in milk of lime, but is insoluble in

all the ordinary alcoholic and ethereal solvents, as well as in

diluted sulphuric acid. The most soluble salt is the hydrochlorate

(C₁₇H₁₉NO₄HCl + H₂O), and that requires 70 parts of water at 20° for

solution. Various salts, such as the sulphate, oxalate, &c., may be

prepared from the hydrochlorate by double decomposition.

Concentrated sulphuric acid dissolves pseudomorphine gradually, with

the production of an olive-green colour.

§ 379. =Opianine= (C₆₆H₇₂N₄O₂₁).--Opianine crystallises in

colourless, glittering ortho-rhombic needles. Ammonia precipitates

it from its solution in hydrochloric acid as a fine white powder. It

is without odour, and has a bitter taste. It is a strong base, and

is soluble in cold, but slightly soluble in boiling water. It is

also but little soluble in boiling alcohol.

An alcoholic solution of the alkaloid gives a voluminous precipitate

with mercuric chloride; after standing a little time, the

precipitate becomes crystalline, the crystals being in the shape of

fine needles. They have the following composition--C₆₆H₇₂N₄O₂₁,

2HCl, 2HgCl--and are with difficulty soluble in water or alcohol.

Opianine, administered to cats in doses of ·145 grm., produces

complex symptoms--_e.g._, dilated pupils, foaming at the mouth,

uncertain gait, paralysis of the hinder extremities, and stupor--but

the alkaloid is rare, and few experiments have been made with it.

§ 380. =Apomorphine= (C₁₇H₁₉NO₃).--Apomorphine is a derivative of

morphine, and is readily prepared by saponifying morphine by heating

it with dilute hydrochloric acid in sealed tubes. The result is

apomorphine hydrochloride, the morphine losing one molecule of

water, according to the equation C₁₇H₁₉NO₃ = C₁₇H₁₇NO₂ + H₂O.

To extract apomorphine, the bases are precipitated by sodic

bicarbonate, and the precipitate extracted by ether or chloroform,

either of which solvents leaves morphine undissolved. The

apomorphine is again converted into hydrochloride, and once more

precipitated by sodic bicarbonate, and is lastly obtained as a

snow-white substance, rapidly becoming green on exposure to the air.

The mass dissolves with a beautiful green colour in water, and also

in alcohol, whilst it colours ether purple-red, and chloroform

violet.

A test for apomorphine is the following:--The chloride is dissolved

in a little acetic acid and shaken with a crystal of potassic iodate

(KIO₃); this immediately turns red from liberated iodine on shaking

it up with a little chloroform; on standing, the chloroform sinks to

the bottom, and is coloured by the alkaloid a beautiful blue colour;

on now carefully pouring a little CS₂ on the surface of the liquid

at the point of junction it is coloured amethyst owing to dissolved

iodine, and apocodeine gives a similar reaction.

Apomorphine is the purest and most active emetic known: whether

injected beneath the skin or taken by the mouth, the effect is the

same--there is considerable depression, faintness, and then

vomiting. The dose for an adult is about 6 mgrms. (·092 grain)

subcutaneously administered.

§ 381. The reactions of some of the rarer alkaloids of opium with

sulphuric acid and ferric chloride are as follows: none of them have

at present any toxicological importance:--

TABLE SHOWING SOME OF THE REACTIONS OF THE RARER ALKALOIDS OF OPIUM.

+---------------+---------+----------------------+----------------+

+---------------+---------+----------------------+----------------+

|Codamine, |C₂₀H₂₅NO₄ {|Dirty red-violet |} |

| | {|colour, turning dark |} Dark green. |

|Landamine, |C₂₀H₂₅NO₄ {|violet on the |} |

| | {|addition of HNO₃. |} |

| | | | |

|Landanosine, |C₂₀H₂₇NO₄ }|Dirty green to |} |

| | }|brownish-green. |} No colour. |

|Protapine, |C₂₀H₁₉NO₅ }| |} |

| | | | |

| | | | |

|Hydrocotarnine,|C₁₂H₁₅NO₃ {|Dirty red-violet; |} |

| | {|not changed by |} No colour. |

| | {|trace of HNO₃. |} |

+---------------+---------+----------------------+----------------+

§ 382. =Tritopine= (C₄₂H₅₄N₂O₇).--This is a rare alkaloid that has

been found in small quantities in opium. It is crystalline,

separating in transparent prisms. Melting-point 182°. It is soluble

in alcohol and chloroform, and slightly soluble in ether.[417]

[417] E. Kander, _Arch. Pharm._, 228, pp. 419-431.

§ 383. =Meconin (Opianyl)= (C₁₀H₁₀O₄) is in the form of white

glittering needles, which melt under water at 77° and in air at 90°,

again coagulating at 75°. It may be sublimed in beautiful crystals.

It is soluble in 22 parts of boiling, and 700 of cold water;

dissolves easily in alcohol, ether, acetic acid, and ethereal oil,

and is not precipitated by acetate of lead. Its solution in

concentrated sulphuric acid becomes, on warming, purple, and gives,

on the addition of water, a brown precipitate. Meconin may be

prepared by treating narcotine with nitric acid. Meconin, in large

doses, is a feeble narcotic; 1·25 grm. (20 grains) has been given to

man without result.

§ 384. =Meconic Acid= (C₇H₄O₇) crystallises in white shining scales

or small rhombic prisms, with three atoms of water (C₇H₄O₇ + 3H₂O),

but at 100° this is lost, and it becomes an opaque white mass. It

reddens litmus, and has a sourish taste. It is soluble in 115 parts

of cold, but dissolves in 4 parts of boiling water; it dissolves

easily in alcohol, less so in ether. It forms well-marked salts; the

barium and calcium salt crystallise with one atom of water, the

former having the composition BaH₄(C₇HO₇)₂; the latter, if ammonium

meconate is precipitated by calcium chloride, CaH₄(C₇HO₇)₂; but if

calcium chloride is added to the acid itself, the salt has the

composition C₇H₂CaO₇ + H₂O. If meconic acid is gently heated, it

decomposes into carbon dioxide and comenic acid (C₆H₄O₅). If the

heat is stronger, pyromeconic acid (C₅H₄O₃)--carbon dioxide, water,

acetic acid, and benzole are formed. Pyromeconic acid is readily

sublimed in large transparent tables. Chloride of iron, and soluble

iron salts generally, give with meconic acid (even in great

dilution) a lively red colour, which is not altered by heat, nor by

the addition of HCl nor by that of gold chloride. Sugar of lead and

nitrate of silver each give a white precipitate; and mercurous and

mercuric nitrates white and yellow precipitates. In any case where

the analyst has found only meconic acid, the question may be raised

in court as to whether it is a poison or not. The early experiments

of Sertürner,[418] Langer, Vogel, Sömmering, and Grape[419] showed

that, in comparatively speaking large doses, it had but little, if

any, action on dogs or men. Albers[420] has, however, experimented

on frogs, and found that in doses of ·1 to ·2 grm. there is, first,

a narcotic action, and later, convulsions and death. According to

Schroff,[421] there is a slight narcotic action on man.

[418] _Ann. Phys._, xxv. 56; xxvii. 183.

[419] _De opio et de illis quibus constat partibus_, Berol., 1822.

[420] _Arch. Path. Anat._, xxvi. 248.

[421] _Med. Jahresb._, 1869.

The most generally accepted view at the present time is that the

physiological action of meconic acid is similar to that of lactic

acid--viz., large doses cause some depression and feeble narcosis.

In a special research amongst organic fluids for meconic acid, the

substances are extracted by alcohol _feebly_ acidulated with nitric

acid; on filtration the alcohol, after the addition of a little water,

is distilled off, and to the remaining fluid a solution of acetate of

lead is added, and the whole filtered. The filtrate will contain any

alkaloids, whilst meconic acid, if present, is bound up with the lead on

the filter. The meconate of lead may be either washed or digested in

strong acetic acid to purify it, suspended in water, and freed from lead

by SH₂; the filtrate from the lead sulphide may be tested by ferric

chloride, or preferably, at once evaporated to dryness, and weighed.

After this operation it is identified. If the quantity is so small that

it cannot be conveniently weighed, it may be estimated colorimetrically,

by having a standard solution of meconic acid, containing 1 mgrm. in

every c.c. A few drops of neutral ferric chloride are added in a Nessler

cylinder to the liquid under examination; and the tint thus obtained is

imitated in the usual way, in another cylinder, by means of ferric

chloride, the standard solution, and water. It is also obvious that the

weight of the meconic acid may be increased by converting it into the

barium salt--100 parts of anhydrous baric meconate, (Ba₂C₇H₂O₇), being

equivalent to 42·3 of meconic acid (C₇H₄O₇).

IV.--The Strychnine or Tetanus-Producing[422] Group of Alkaloids.

[422] To this group also belong some of the opium alkaloids. See

“Thebaine,” “Landamine,” “Codeine,” “Hydrocotarnine.”

1. NUX VOMICA GROUP--STRYCHNINE--BRUCINE--IGASURINE.

§ 385. Nux vomica is found in commerce both in the entire state and as a

powder. It is the seed of the _Strychnos nux vomica_, or Koochla tree.

The seed is about the size of a shilling, round, flattened,

concavo-convex, of a yellowish-grey or light-brown colour, covered with

a velvety down of fine, radiating, silky hairs, which are coloured by a

solution of iodine beautiful gold-yellow; the texture is tough,

leathery, and not easily pulverised; the taste is intensely bitter. The

powder is not unlike that of liquorice, and, if met with in the pure

state, gives a dark orange-red colour with nitric acid, which is

destroyed by chloride of tin; the aqueous infusion gives a precipitate

with tincture of galls, is reddened by nitric acid, and gives an

olive-green tint with persulphate of iron. The best method, however, of

recognising quickly and with certainty that the substance under

examination is nux vomica powder, is to extract strychnine from it by

the following simple process:--The powder is completely exhausted by

boiling alcohol (90 per cent.), the alcoholic extract evaporated to

dryness, and then treated with water; the aqueous solution is passed

through a wet filter, and concentrated by evaporation to a small bulk.

To this liquid a drop or so of a concentrated solution of picric acid is

added, and the yellow precipitate of picrates thus obtained is

separated, treated with nitric acid, the picric acid removed by ether,

and the pure alkaloid precipitated by soda, and shaken out by

chloroform.

§ 386. =Chemical Composition.=--Nux vomica contains at least four

distinct principles:--

(1.) Strychnine.

(2.) Brucine.

(3.) Igasurine.

(4.) Strychnic or igasuric acid.

§ 387. =Strychnine= (C₂₁H₂₂N₂O₂) is contained in the bean of S.

_ignatius_, in the bark (_false angustura bark_) and seeds of the

_Strychnos nux vomica_, in the _Strychnos colubrina_, L., in the

_Strychnos tieuté_, Lesch, and probably in various other plants of the

same genus.

Commercial strychnine is met with either in colourless crystals or as a

white powder, the most usual form being that of the alkaloid itself; but

the nitrate, sulphate, and acetate are also sold to a small extent.

The _microscopical appearance_ of strychnine, as thrown down by the

solution of vapour of ammonia, may be referred to three leading

forms--the long rectangular prism, the short hexagonal prism, or the

regular octahedron. If obtained from the slow evaporation of an

alcoholic solution, it is usually in the form of four-sided pyramids or

long prisms; but if obtained by speedy evaporation or rapid cooling, it

appears as a white granular powder. If obtained from a benzene solution,

the deposit is usually crystalline, but without a constant form, though

at times the crystals are extremely distinct, the short six-sided prism

prevailing; but triangular plates, dodecahedral, rhomboidal, and

pentagonal, may also be met with. An ethereal solution on evaporation

assumes dendritic forms, but may contain octahedra and four-sided

prisms. A chloroform solution deposits rosettes, veined leaves, stellate

dotted needles, circles with broken radii, and branched and reticulated

forms of great delicacy and beauty.--_Guy._

Strychnine is very insoluble in water, although readily dissolved by

acidulated water. According to Wormley’s repeated experiments, one part

of strychnine dissolves in 8333 parts of cold water; and, according to

Pelletier and Cahours, it dissolves in 6667 parts of cold, and 2500

parts of boiling water. It may be convenient, then, to remember that a

gallon of cold water would hardly dissolve more than 10 grains (·142

grm. per litre); the same amount, if boiling, about 30 grains (·426 grm.

per litre) of strychnine. The solubility of one part of strychnine in

other menstrua is as follows:--Cold alcohol, 0·833 specific gravity,

120, boiling, 10 parts (_Wittstein_); cold alcohol, 0·936 specific

gravity, 240 parts (_Merck_); cold alcohol, 0·815 specific gravity, 107

parts (_Dragendorff_); amyl alcohol, 181 parts; benzene, 164;

chloroform, 6·9 (_Schlimpert_), 5 (_Pettenkofer_); ether, 1250 parts;

carbon disulphide, 485 parts; glycerin, 300 parts. Creosote and

essential and fixed oils also dissolve strychnine.

Of all the above solvents, it is evident that chloroform is the best for

purposes of separation, and next to chloroform, benzene.

If a speck of strychnine be placed in the subliming cell, it will be

found to sublime usually in a crystalline form at 169°. A common form at

this temperature, according to the writer’s own observations, is minute

needles, disposed in lines; but, as Dr. Guy has remarked, the sublimate

may consist of drops, of waving patterns, and various other forms; and,

further, while the sublimates of morphia are made up of curved lines,

those of strychnine consist of lines either straight or slightly

curved, with parallel feathery lines at right angles. On continuing the

heat, strychnine melts at about 221°, and the lower disc, if removed and

examined, is found to have a resinous residue; but it still continues to

yield sublimates until reduced to a spot of carbon. The melting-point

taken in a tube is 268°.

Strychnine is so powerfully bitter, that one part dissolved in 70,000 of

water is distinctly perceptible; it is a strong base, with a marked

alkaline reaction, neutralising the strongest acids fully, and

precipitating many metallic oxides from their combinations, often with

the formation of double salts. Most of the salts of strychnine are

crystalline, and all extremely bitter. Strychnine, in the presence of

oxygen, combines with SH₂ to form a beautiful crystalline compound:--

2C₂₁H₂₂N₂O₂ + 6H₂S + O₃ = 2C₂₁H₂₂N₂O₂3H₂S₂ + 3H₂O.

On treatment with an acid this compound yields H₂S₂.--Schmidt, _Ber.

Deutsch. Chem. Ges._, 8, 1267.

An alcoholic solution of strychnine turns the plane of polarisation to

the left, [α]_r_ = -132·08° to 136·78° (_Bouchardat_); but acid

solutions show a much smaller rotatory power.

The salts used in medicine are--the _sulphate_, officinal only in the

French pharmacopœia; the _nitrate_, officinal in the German, Austrian,

Swiss, Norse, and Dutch pharmacopœias; and the _acetate_, well known in

commerce, but not officinal.

The commercial =Sulphate= (C₂₁H₂₂N₂O₂H₂SO₄ + 2H₂O) is an acid salt

crystallising in needles which lose water at 150°, the neutral sulphate

(2C₂₁H₂₂N₂O₂,H₂SO₄ + 7H₂O) crystallises in four-sided, orthorhombic

prisms, and is soluble in about 50 parts of cold water.

The =Nitrate= (C₂₁H₂₂N₂O₂,HNO₃) crystallises on evaporation from a warm

solution of the alkaloid in dilute nitric acid, in silky needles, mostly

collected in groups. The solubility of this salt is considerable, one

part dissolving in 50 of cold, in 2 of boiling water; its solubility in

boiling and cold alcohol is almost the same, taking 60 of the former and

2 of the latter.

The =Acetate= crystallises in tufts of needles; as stated, it is not

officinal in any of the European pharmacopœias.

The chief precipitates or sparingly soluble crystalline compounds of

strychnine are--

(1.) =The Chromate of Strychnine= (C₂₁H₂₂N₂O₂CrHO₂), formed by adding a

neutral solution of chromate of potash to a solution of a strychnine

salt, crystallises out of hot water in beautiful, very insoluble,

orange-yellow needles, mixed with plates of various size and thickness.

The salt is of great practical use to the analyst; for by its aid

strychnine may be separated from a variety of substances, and in part

from brucine--the colour tests being either applied direct to the

strychnine chromate, or the chromate decomposed by ammonia, and the

strychnine recovered from the alkaline liquid by chloroform.

(2.) =Sulphocyanide of Strychnine= (C₂₁H₂₂N₂O₂CNHS) is a thick, white

precipitate, produced by the addition of a solution of potassic

sulphocyanide to that of a strychnine salt; on warming it dissolves, but

on cooling reappears in the form of long silky needles.

(3.) =Double Salts.=--The platinum compound obtained by adding a

solution of platinic chloride to one of strychnine chloride has the

composition C₂₁H₂₂N₂O₂HClPtCl₂, and crystallises out of weak boiling

alcohol (in which it is somewhat soluble) in gold-like scales. The

similar palladium compound (C₂₁H₂₂N₂O₂HCl,PdCl) is in dark brown

needles, and the gold compound (C₂₁H₂₂N₂O₂HClAuCl₃) in orange-coloured

needles.

(4.) =Strychnine Trichloride.=--The action of chlorine on strychnine--by

which chlorine is substituted for a portion of the hydrogen--has been

proposed as a test. The alkaloid is dissolved in very dilute HCl, so as

to be only just acid; on now passing through chlorine gas, a white

insoluble precipitate is formed, which may be recrystallised from ether;

it has probably the composition C₂₁H₁₉Cl₃N₂O₂, and is extremely

insoluble in water.

(5.) =The Iodide of Strychnine= (C₂₁H₂₂N₂O₂HI₃) is obtained by the

action of iodine solution on strychnine sulphate; on solution of the

precipitate in alcohol, and evaporation, it forms violet-coloured

crystals, very similar to those of potassic permanganate.

§ 388. =Pharmaceutical and other Preparations of Nux Vomica and

Strychnine, with Suggestions for their Valuation.=

=An aqueous extract of nux vomica=, officinal in the German

pharmacopœia, appears to contain principally brucine, with a small

percentage of strychnine; the proportion of brucine to strychnine being

about four-fifths to one-fifth. Blossfield found in a sample 4·3 per

cent. of total alkaloid, and two samples examined by Grundmann consisted

(No. 1) of strychnine, 0·6 per cent.; brucine, 2·58 per cent.--total,

3·18 per cent.; (No. 2) strychnine, 0·68 per cent.; brucine, 2·62 per

cent.--total, 3·3 per cent. A sample examined by Dragendorff

yielded--strychnine, 0·8 per cent.; brucine, 3·2 per cent.--total, 4 per

cent. The maximum medicinal dose is put at ·6 grm. (9⁹⁄₁₄ grains).

=The spirituous extract of nux vomica=, officinal in the British and all

the Continental pharmacopœias, differs from the aqueous in containing a

much larger proportion of alkaloids, viz., about 15 per cent., and about

half the total quantity being strychnine. The medicinal dose is

21·6-64·8 mgrms. (⅓ grain to a grain).

There is also an =extract of St. Ignatius bean= which is used in the

United States; nearly the whole of its alkaloid may be referred to

strychnine.

=The tincture of nux vomica=, made according to the British

Pharmacopœia, contains in 1 fl. oz. 1 grain of alkaloids, or 0·21 part

by weight in 100 by volume, but the strength of commercial samples often

varies. Lieth found in one sample 0·122 per cent. of strychnine and 0·09

per cent. brucine; and two samples examined by Wissel consisted

respectively of 0·353 per cent. and 0·346 per cent. of total alkaloids.

Dragendorff found in two samples ·2624 per cent. and ·244 per cent. of

total alkaloids, about half of which was strychnine.

=Analysis.=--Either of the extracts may be treated for a few hours on

the water-bath, with water acidulated by sulphuric acid, filtered, the

residue well washed, the acid liquid shaken up with benzene to separate

impurities, and, on removal of the benzene, alkalised with ammonia, and

shaken up two or three times with chloroform; the chloroform is then

evaporated in a tared vessel, and the total alkaloids weighed. The

alkaloids can then be either (_a_) treated with 11 per cent. of nitric

acid on the water-bath until all the brucine is destroyed, and then (the

liquid being neutralised) precipitated by potassic chromate; or (_b_)

the alkaloids may be converted into picrates. Picrate of strychnine is

very insoluble in water, 1 part requiring no less than 10,000 of

water.[423] The tincture is analysed on precisely similar principles,

the spirit being got rid of by distillation, and the residue treated by

acidified water, &c.

[423] Dolzler, _Arch. Pharm._ [3], xxiv. 105-109.

The nux vomica powder itself may be valued as follows:--15 to 20 grms.,

pulverised as finely as possible, are treated three times with 150 to

300 c.c. of water, acidified with sulphuric acid, well boiled, and,

after each boiling, filtered and thoroughly pressed. The last exhaustion

must be destitute of all bitter taste. The united filtrates are then

evaporated to the consistence of a thick syrup, which is treated with

sufficient burnt magnesia to neutralise the acid. The extract is now

thoroughly exhausted with boiling alcohol of 90 per cent.; the alcoholic

extract, in its turn, is evaporated nearly to dryness, and treated with

acidulated water; this acid solution is freed from impurities by shaking

up with benzene, and lastly alkalised with ammonia, and the alkaloids

extracted by shaking up with successive portions of chloroform. The

chloroformic extract equals the total alkaloids, which may be separated

in the usual way.

In four samples of nux vomica examined by Dragendorff, the total

alkaloids ranged from 2·33 to 2·42 per cent. Grate found in two samples

2·88 per cent. and 2·86 per cent. respectively; while Karing from one

sample separated only 1·65 per cent. The strychnine and brucine are in

about equal proportions, Dragendorff[424] finding 1·187 per cent.

strychnine and 1·145 per cent. brucine.[425]

[424] Dragendorff, _Die chemische Werthbestimmung einiger starkwirkenden

Droguen_, St. Petersburg, 1874.

[425] These details are very necessary, as bearing on the question of

the fatal dose of nux vomica, which Taylor tells us (_Med. Jurisprud._,

i. 409) was of some importance in _Reg._ v. _Wren_, in which 47 grains

were attempted to be given in milk. The fatal dose of nux vomica must be

ruled by its alkaloidal content, which may be so low as 1 per cent., and

as high as nearly 3 per cent. 30 grains have proved fatal (_Taylor_); if

the powder in this instance was of the ordinary strength, the person

died from less than a grain (·0648 grm.) of the united alkaloids.

The =vermin-killers= in use in this country are those of Miller, Battle,

Butler, Clift, Craven, Floyd, Gibson, Hunter, Stenier, and Thurston. Ten

samples from these various makers were examined recently by Mr. Allen

(_Pharm. Journal_, vol. xii., 1889), and the results of the analyses are

embodied in the following table:--

+-----+----------+------+-------------------+-------+--------------+

+-----+----------+------+---------+---------+-------+--------------+

| | | | | | | |

| 1 | 5·6 | 3_d._| 0·61 | 10·9 | Wheat | ? |

| 2 | 11·8 | 3_d._| 0·80 | 6·7 | Wheat | Ultramarine. |

| 3 | 13·1 | 3_d._| 1·12 | 8·7 | Rice | Ultramarine. |

| 4 | 11·6 | 3_d._| 1·28 | 11·1 | Rice | Ultramarine. |

| 5 | 13·1 | 3_d._| 1·70 | 13·0 | Rice | Ultramarine. |

| 6 | 21·5 | 6_d._| 2·42 | 11·2 | Wheat |Prussian blue.|

| 7 | 49·2 | 3_d._| 2·85 | 5·8 | Wheat | Soot. |

| 8 | 30·5 | 3_d._| 3·45 | 11·3 | Wheat |Prussian blue.|

| 9 | 16·6 | 3_d._| 3·81 | 19·4 | Rice | Carmine. |

| 10 | 10·0 | 3_d._| 4·18 | 41·8 | Rice | Ultramarine. |

+-----+----------+------+---------+---------+-------+--------------+

§ 389. =Statistics.=--In England, during the ten years 1883-92, out of

6666 total deaths from poison, strychnine, nux vomica, and vermin-killer

account for 325. Out of these deaths, 118 were ascribed to

“vermin-killer.” “Vermin-killer” may be presumed to include not only

strychnine mixtures, but also phosphorus and arsenic pastes and powders,

so that there are no means of ascertaining the number of strychnine

cases comprised under this heading. Taking the deaths actually

registered as due to strychnine or nux vomica, they are about 4·7 per

cent. of the deaths from all sorts of poison. Of these deaths, 268, or

82·4 per cent., were suicidal, 8 were homicidal, and 49 only were

accidental.

Schauenstein has collected from literature 130 cases of poisoning by

strychnine, but most of these occurred during the last twenty-five

years; 62 of the 130, or about one-half, were fatal, and 15 were

homicidal. It has been stated that strychnine is so very unsuitable for

the purpose of criminal poisoning as to render it unlikely to be often

used. Facts, however, do not bear out this view; for, allowing its

intensely bitter taste, yet it must be remembered that bitter liquids,

such as bitter ale, are in daily use, and a person accustomed to drink

any liquid rapidly might readily imbibe sufficient of a toxic liquid to

produce death before he was warned by its bitterness. It is, indeed,

capable of demonstration, that taste is more vivid _after_ a substance

has been taken than just in the act of swallowing, for the function of

taste is not a rapid process, and requires a very appreciable interval

of time.

The series of murders by Thomas Neill, or, more correctly, Thomas Neill

Cream, is an example of the use of strychnine for the purposes of

murder. Thomas Neill Cream was convicted, October 21, 1892, for the

murder of Matilda Clover on October 20, 1891; there was also good

evidence that the same criminal had murdered Ellen Dunworth, October 13,

1891; Alice Marsh, April 12, 1892; Emma Shrivell, April 12, 1892, and

had attempted the life of Louie Harvey. The agent in all these cases was

strychnine. There was no evidence as to what form of the poison was

administered in the case of Clover, but Ellen Dunworth, who was found

dying in the streets at 7.45 P.M., and died less than two hours

afterwards, stated that a gentleman gave her “two drops” of white stuff

to drink.

In the cases of Marsh and Shrivell, Neill Cream had tea with them on the

night of April 11, and gave them both “three long pills;” half an hour

after Neill Cream left them they were found to be dying, and died within

six hours. From Marsh 7 grains, from Shrivell nearly 2 grains of

strychnine were separated; the probability is that each pill contained

at least 3 grains of strychnine. The criminal met Louie Harvey on the

Embankment, and gave her “some pills” to take; she pretended to do so,

but threw them away. Hence it seems probable that Neill Cream took

advantage of the weakness that a large number of the population have for

taking pills, and mostly poisoned his victims in this manner. Clover’s

case was not diagnosed during life, but strychnine was found six or

seven months after burial in the body. It may be mentioned incidentally

that the accused himself furnished the clue which led to his arrest, by

writing letters charging certain members of the medical profession with

poisoning these poor young prostitutes with strychnine.

§ 390. =Fatal Dose.=--In a research, which may, from its painstaking

accuracy, be called classical, F. A. Falck has thrown much light upon

the minimum lethal dose of strychnine for various animals. It would seem

that, in relation to its size, the frog is by no means so sensible to

strychnine as was believed, and that animals such as cats and rabbits

take a smaller dose in proportion to their body-weight. The method used

by Falck was to inject subcutaneously a solution of known strength of

strychnine nitrate, and, beginning at first with a known lethal dose, a

second experiment was then made with a smaller dose, and if that proved

fatal, with a still smaller, and so on, until such a quantity was

arrived at, that the chances as determined by direct observation were as

great of recovery as of death. Operating in this way, and making no less

than 20 experiments on the rabbit, he found that the least fatal dose

for that animal was ·6 mgrm. of strychnine nitrate per kilogramme. Cats

were a little less susceptible, taking ·75 mgrm. Operating on fowls, he

found that strychnine taken into the crop in the usual way was very

uncertain; 50 mgrms. per kilo, taken with the food had no effect, but

results always followed if the poison was introduced into the

circulation by the subcutaneous needle--the lethal dose for fowls being,

under those circumstances, 1 to 2 mgrms. per kilo. He made 35

experiments on frogs, and found that to kill a frog by strychnine

nitrate, at least 2 mgrms. per kilo, must be injected. Mice take a

little more, from 2·3 to 2·4 mgrms. per kilo. In 2 experiments on the

ring adder, in one 62·5 mgrms. per kilo. of strychnine nitrate, injected

subcutaneously, caused death in seven hours; in the second, 23·1 mgrms.

per kilo. caused death in five days; hence the last quantity is probably

about the least fatal dose for this particular snake.

These observations may be conveniently thrown into the following table

(see next page), placing the animals in order according to their

relative sensitiveness.[426]

[426] According to Christison’s researches, 0·2 grm. (about ⅓ grain) is

fatal to swine; ·03 grm. (½ grain) to bears, if injected into the

pleura. 1 to 3 grains (·0648 to ·1944 grm.) is given to horses in cases

of paralysis, although 3 grains cannot but be considered a dangerous

dose, unless smaller doses have been previously administered without

effect; 10 grains would probably kill a horse, and 15 grains (·972 grm.)

have certainly done so.

Now, the important question arises, as to the place in this series

occupied by man--a question difficult to solve, because so few cases are

recorded in which strychnine has been administered by subcutaneous

injection with fatal result. Eulenberg has observed poisonous symptoms,

but not death, produced by 6 mgrms. (1/11 grain) and by 10 mgrms. (about

⅙ grain). Bois observed poisonous symptoms from the similar subcutaneous

administrations of 8 mgrms. to a child six years old, and 4 mgrms. to

another child four years old--the latter dose, in a case recorded by

Christison, actually killing a child of three years of age. On the other

hand, the smallest lethal dose taken by an adult was swallowed in

solution. Dr. Warner took 32 mgrms. (½ grain) of strychnine sulphate,

mistaking it for morphine sulphate, and died in twenty minutes. In other

cases 48 mgrms. (7/10 grain) have been fatal. It will be safe to

conclude that these doses by the stomach would have acted still more

surely and energetically if injected subcutaneously. The case of Warner

is exceptional, for he was in weak health; and, if calculated out

according to body-weight, presuming that Dr. Warner weighed 68 kilos.,

the relative dose as strychnine nitrate would be ·24 per kilo.--a

smaller dose than for any animal hitherto experimented upon. There is,

however, far more reason for believing that the degree of sensitiveness

in man is about the same as that of cats or dogs, and that the least

fatal dose for man is ·70 per kilo., the facts on record fairly bearing

out this view. It is, therefore, probable that death would follow if 38

mgrms. (7/10 grain) were injected subcutaneously into a man of the

average weight of 68 kilos. (150 lbs.). Taylor estimates the fatal dose

of strychnine for adults as from 32·4 to 129·6 mgrms. (·5 to 2 grains);

Guy puts the minimum at 16·2 mgrms. (·25 grain).

TABLE SHOWING THE ACTION OF STRYCHNINE ON ANIMALS.

+------------+----------------------+--------------------------------+

| | | Reckoned on 1 Kilo. of |

| | | Body-weight. |

| | +-----------------|--------------+

| | +-----------------+--------------+

| | | Dose of Strychnine Nitrate in |

| | | Mgrms. |

+------------+----------------------+-----------------+--------------+

| Rabbit, | Subcutaneous. | 0·50 | 0·60 |

| Cat, | „ | ... | 0·75 |

| Dog, | „ | ... | 0·75 |

| „ | Taken by the Stomach.| 2·0 | 3·90 |

| „ | „ Rectum. | ... | 2·00 |

| „ | „ Bladder.| 5·50 | ... |

| Fox, | Subcutaneous. | ... | 1·00 |

| Hedgehog, | „ | 1·00 | 2·00 |

| Fowl, | „ | ... | 2·00 |

| Frog, | „ | 2·00 | 2·10 |

| Mouse, | „ | 2·36 | 2·36 |

| Ring Adder,| „ | ... | 23·10 |

+------------+----------------------+-----------------+--------------+

Large doses of strychnine may be recovered from if correct medical

treatment is sufficiently prompt. Witness the remarkable instances on

record of duplex poisonings, in which the would-be-suicide has

unwittingly defeated his object by taking strychnine simultaneously with

some narcotic, such as opium or chloral. In a case related by

Schauenstein,[427] a suicidal pharmacist took ·48 grm. or ·6 grm. (7·4

to 9·25 grains) of strychnine nitrate dissolved in about 30 c.c. of

bitter-almond water, and then, after half an hour, since no symptoms

were experienced, ·6 grm. (9·25 grains) of morphine acetate, which he

likewise dissolved in bitter-almond water and swallowed. After about ten

minutes, he still could walk with uncertain steps, and poured some

chloroform on the pillow-case of his bed, and lay on his face in order

to breathe it. In a short time he lost consciousness, but again awoke,

and lay in a half-dreamy state, incapable of motion, until some one

entered the room, and hearing him murmur, came to his bedside. At that

moment--two and a quarter hours after first taking the strychnine--the

pharmacist had a fearful convulsion, the breathing was suspended, and he

lost consciousness. Again coming to himself, he had several convulsions,

and a physician who was summoned found him in general tetanus. There

were first clonic, then tonic convulsions, and finally opisthotonus was

fully developed. The treatment consisted of emetics, and afterwards

tannin and codeine were given separately. The patient slept at short

intervals; in ten hours after the taking of the poison the seizures were

fewer in number and weaker in character, and by the third day recovery

was complete. Dr. Macredy[428] has also placed on record an interesting

case, in which the symptoms, from a not very large dose of strychnine,

were delayed by laudanum for eight hours. A young woman, twenty-three

years of age, pregnant, took at 10 A.M. a quantity of strychnine

estimated at 1·5 grain, in the form of Battle’s vermin-killer, and

immediately afterwards 2 ounces of laudanum. She was seen by Dr. Macredy

in four hours, and was then suffering from pronounced narcotic symptoms.

A sulphate of zinc emetic was administered. In eight hours after taking

the strychnine, there were first observed some clonic convulsive

movements of the hands, and, in a less degree, the legs. These

convulsions continued, at times severe, for several hours, and were

treated with chloral. Recovery was speedy and complete.

[427] Maschka’s _Handbuch_, from Tschepke, _Deutsche Klinik_, 1861.

[428] _Lancet_, November 28, 1882.

In a similar case related by Dr. Harrison,[429] a man, aged 54, took a

packet of Battle’s vermin-killer, mixed with about a drachm and a half

of laudanum and some rum. At the time he had eaten no food for days, and

had been drinking freely; yet fifty minutes elapsed before the usual

symptoms set in, and no medical treatment was obtained until four hours

after taking the dose. He was then given chloral and other remedies, and

made a rapid recovery.

[429] _Lancet_, May 13, 1882.

§ 391. =Action on Animals.=--The action of strychnine has been

experimentally studied on all classes of animals, from the infusoria

upwards. The effects produced on animal forms which possess a nervous

system are strikingly alike, and even in the cephalopoda, tetanic

muscular spasm may be readily observed. Of all animals the frog shows

the action of strychnine in its purest form, especially if a dose be

given of just sufficient magnitude to produce toxic effects. The frog

sits perfectly still and quiet, unless acted upon by some external

stimuli, such as a breath of air, a loud noise, or the shaking of the

vessel which contains it, then an immediate tetanic convulsion of all

the muscles is witnessed, lasting a few seconds only, when the animal

again resumes its former posture. This heightened state of reflex action

has its analogue in hydrophobia as well as in idiopathic tetanus. If the

frog thus poisoned by a weak dose is put under a glass shade, kept

moist, and sheltered from sound, or from other sources of irritation, no

convulsions occur, and after some days it is in its usual health. If, on

the other hand, by frequent stimuli, convulsions are excited, the animal

dies. M. Richet[430] has contributed a valuable memoir to the Academy of

Sciences on the toxic action of strychnine. He has confirmed the

statement of previous observers that, with artificial respiration, much

larger doses of strychnine may be taken without fatal result than under

normal conditions, and has also recorded some peculiar phenomena.

Operating on dogs and rabbits, after first securing a canula in the

trachea, and then injecting beneath the skin or into the saphena vein 10

mgrms. of strychnine hydrochlorate, the animal is immediately, or within

a few seconds, seized with tetanic convulsions, and this attack would be

mortal, were it not for artificial respiration. Directly this is

practised the attack ceases, and the heart, after a period of hurried

and spasmodic beats, takes again its regular rhythm. Stronger and

stronger doses may then be injected without causing death. As the dose

is thus augmented, the symptoms differ. M. Richet distinguishes the

following periods:--(1.) A period of tetanus. (2.) A period of

convulsion, characterised by spasmodic and incessant contraction of all

the muscles. (3.) A little later, when the quantity exceeds 10 mgrms.

per kilo., a choreic period, which is characterised by violent rhythmic

shocks, very sudden and short, repeated at intervals of about three to

four seconds; during these intervals there is almost complete

relaxation. (4.) A period of relaxation; this period is attained when

the dose exceeds 40 mgrms. per kilo. Reflex action is annihilated, the

spontaneous respiratory movements cease, the heart beats tumultuously

and regularly in the severe tetanic convulsions at first, and then

contracts with frequency but with regularity. The pupils, widely dilated

at first, become much contracted. The arterial pressure, enormously

raised at the commencement, diminishes gradually, in one case from 0·34

mm. to 0·05 mm. The temperature undergoes analogous changes, and during

the convulsions is extraordinarily elevated; it may even attain 41° or

42°, to sink in the period of relaxation to 36°. Dogs and rabbits which

have thus received enormous quantities of strychnine (_e.g._, 50 mgrms.

per kilo.), may, in this way, live for several hours, but the slightest

interruption to the artificial respiration, in the relaxed state, is

followed by syncope and death.

[430] _De l’Action de la Strychnine à très forte dose sur les

Mammifères. Comptes Rend._, t. xcl. p. 131.

§ 392. =Effects on Man: Symptoms.=--The commencement of symptoms may be

extremely rapid, the rapidity being mainly dependent on the form of the

poison and the manner of application. A soluble salt of strychnine

injected subcutaneously will act within a few seconds;[431] in a case of

amaurosis, related by Schuler,[432] 5·4 mgrms. of a soluble strychnine

salt were introduced into the punctum lachrymale;--in less than four

minutes there were violent tetanic convulsions. In a case related by

Barker, the symptoms commenced in three minutes from a dose of ·37 grm.

(5·71 grains).[433] Here the poison was not administered subcutaneously.

Such short periods, to a witness whose mind was occupied during the

time, might seem immediate. On the other hand, when nux vomica powder

has been taken, and when strychnine has been given in the form of pill,

no such rapid course has been observed, or is likely to occur, the usual

course being for the symptoms to commence within half an hour. It is,

however, also possible for them to be delayed from one to two hours, and

under certain circumstances (as in the case related by Macredy) for

eight hours. In a few cases, there is first a feeling of uneasiness and

heightened sensibility to external stimuli, a strange feeling in the

muscles of the jaw, and a catching of the respiration; but generally

the onset of the symptoms is as sudden as epilepsy, and previous to

their appearance the person may be pursuing his ordinary vocation, when,

without preliminary warning, there is a shuddering of the whole frame,

and a convulsive seizure. The convulsions take the form of violent

general tetanus; the limbs are stretched out involuntarily, the hands

are clenched, the soles of the feet incurved, and, in the height of the

paroxysm, the back may be arched and rigid as a board, the sufferer

resting on head and heels, and the abdomen tense. In the grasp of the

thoracic muscles the walls of the chest are set immovable, and from the

impending suffocation the face becomes congested, the eyes prominent and

staring. The muscles of the lower jaw--in “disease tetanus” the first to

be affected--are in “strychnos tetanus,” as a rule, the last; a

distinction, if it were more constant, of great clinical value. The

convulsions and remissions recur until death or recovery, and, as a

rule, within two hours from the commencement of the symptoms the case in

some way or other terminates. The number of the tetanic seizures noted

has varied--in a few cases the third spasm has passed into death, in

others there have been a great number. The duration of the spasm is also

very different, and varies from thirty seconds to five or even eight

minutes, the interval between lasting from forty-five seconds[434] to

one or even one and a half hours.[435]

[431] In one of M. Richet’s experiments, a soluble strychnine salt

injected into a dog subcutaneously acted in fourteen seconds.

[432] Quoted by Taylor from _Med. Times and Gazette_, July, 1861.

[433] A non-fatal dose may show its effects rapidly, _e.g._, there is a

curious case of symptoms of poisoning caused by the _last_ dose of a

mixture which is recorded in _Pharm. Journ._, 1893, 799. A medical

practitioner prescribed the following mixture:--

℞. Tr. strophanthi, ʒi.

Liq. strychni hydrochlorici, ʒiiss.

Sol. bismuthi et pepsin. (Richardson’s), ℥iss.

Sp. ammon. aromat., ...

Sp. chloroformi, aa. ℥iss.

Aquam ad, ℥vi.

ft. mist.

Shake the bottle.

Two teaspoonfuls when the attack threatens, and repeat in an hour if

necessary.

Richardson’s liquor bismuth contains 1/20 grain of strychnine in each

drachm. The mixture was alkaline; it contained 1·7 grain of strychnine

and 38·25 minims of chloroform.

The patient, a woman, 54 years of age, had taken the previous doses with

considerable relief; but ten minutes after the last dose, which she

described as far more bitter than those she had taken previously, she

was seized with the usual symptoms of strychnine poisoning, but

recovered after five hours.

The explanation is pretty obvious; the mixture was alkaline, so that the

strychnine was not in the form of a salt, but in the free state, and was

therefore dissolved by the chloroform; the amount of strychnine taken in

each dose wholly depended on whether or not the mixture was shaken

violently and poured out into the teaspoon immediately after shaking; if

allowed to repose the globules of chloroform saturated with strychnine

would settle at the bottom, and there form a stratum rich in strychnine;

so that the last dose would certainly contain an excess.

[434] White, _Brit. Med. Journ._, 1867.

[435] Folkes, _Med. Times_, 1869.

§ 393. =Diagnosis of Strychnine Poisoning.=--However striking and well

defined the picture of strychnine tetanus may be, mistakes in diagnosis

are rather frequent, especially when a medical man is hastily summoned,

has never seen a case of similar poisoning, and has no suspicion of the

possible nature of the seizure. If a young woman, for instance, is the

subject, he may put it down to hysteria, and certainly hysteria not

unfrequently affects somewhat similar convulsions. In a painful case in

which the author was engaged, a young woman either took or was given

(for the mystery was never cleared up fully) a fatal dose of strychnine,

and though the symptoms were well marked, the medical attendant was so

possessed with the view that the case was due to hysteria, that, even

after making the _post-mortem_ examination, and finding no adequate

lesion, he theorised as to the possibility of some fatal hysteric spasm

of the glottis, while there was ample chemical evidence of strychnine,

and a weighable quantity of the alkaloid was actually separated from the

contents of the stomach. The medical attendant of Matilda Clover, one of

Neill’s victims, certified that the girl died from _delirium tremens_

and syncope, although the symptoms were typically those produced by

strychnine. Such cases are particularly sad, for we now know that, with

judicious treatment, a rather large dose may be recovered from.

If the case is a male, a confusion with epilepsy is possible, though

hardly to be explained or excused; while in both sexes idiopathic

tetanus is so extremely similar as to give rise to the idea that all

cases of idiopathic tetanus are produced by poison, perhaps secreted by

the body itself. As for the distinction between idiopathic and strychnic

tetanus, it is usually laid down (1) that the intervals in the former

are characterised by no relaxation of the muscles, but that they

continue contracted and hard; and (2) that there is a notable rise of

temperature in disease tetanus proper, and not in strychnine tetanus.

Both statements are misleading, and the latter is not true, for in

strychnic poisoning the relaxation is not constant, and very high

temperatures in animals have been observed.

§ 394. =Physiological Action.=--The tetanic convulsions are essentially

reflex, and to be ascribed to a central origin; the normal reflex

sensibility is exaggerated and unnaturally extended. If the ischiatic

plexus supplying the one leg of an animal is cut through, that leg takes

no part in the general convulsions, but if the artery of the leg alone

is tied, then the leg suffers from the muscular spasm, as well as the

limbs in which the circulation is unrestrained. In an experiment by Sir

B. W. Richardson, a healthy dog was killed, and, as soon as practicable,

a solution of strychnine was injected through the systemic vessels by

the aorta--the whole body became at once stiff and rigid as a board.

These facts point unmistakably to the spinal marrow as the seat of the

toxic influence. Strychnine is, _par excellence_, a spinal poison. On

physiological grounds the grey substance of the cord is considered to

have an inhibitory action upon reflex sensibility, and this inhibitory

power is paralysed by strychnine. The spinal cord, it would appear, has

the power of collecting strychnine from the circulation and storing it

up in its structure.[436]

[436] R. W. Lovett, _Journ. Physiol._, ix. 99-111.

Much light has been thrown upon the cause of death by Richet’s

experiments.[437] It would seem that, in some cases, death takes place

by a suffocation as complete as in drowning, the chest and diaphragm

being immovable, and the nervous respiratory centres exhausted. In such

a case, immediate death would be averted by a tracheal tube, by the aid

of which artificial respiration might be carried on; but there is

another asphyxia due to the enormous interstitial combustion carried on

by muscles violently tetanised. “If,” says Richet, “after having

injected into a dog a mortal dose of strychnine, and employed artificial

respiration according to the classic method twenty or thirty times a

minute, the animal dies (sometimes at the end of ten minutes, and in

every case at the end of an hour or two), and during life the arterial

blood is examined, it will be ascertained that it is black, absolutely

like venous blood.”

[437] _Op. cit._

This view is also supported by the considerable rise of temperature

noticed: the blood is excessively poor in oxygen, and loaded with carbon

dioxide. That this state of the blood is produced by tetanus, is proved

by the fact that an animal poisoned by strychnine, and then injected

subcutaneously with curare in quantity just sufficient to paralyse the

muscular system, does not exhibit these phenomena. By the aid of

artificial respiration, together with the administration of curare, an

animal may live after a prodigious dose of strychnine.

Meyer[438] has investigated carefully the action of strychnine on the

blood-pressure--through a strong excitement of the vaso-motor centre,

the arteries are narrowed in calibre, and the blood-pressure much

increased; the action of the heart in frogs is slowed, but in the

warm-blooded animals quickened.

[438] _Wiener Akad. Sitzungsber._, 1871.

§ 395. =Post-mortem Appearances.=--There is but little characteristic in

the _post-mortem_ appearances from strychnine poisoning. The body

becomes very stiff a short time after death, and this rigidity remains

generally a long time. In the notorious Palmer case, the body was rigid

two months after death, but, on the other hand, the _rigor mortis_ has

been known to disappear within twenty-four hours. If the convulsions

have been violent, there may be minute hæmorrhages in the brain and

other parts. I have seen considerable hæmorrhage in the trachea from

this cause. When death occurs from asphyxia, the ordinary signs of

asphyxia will be found in the lungs, &c. The heart mostly has its right

side gorged with blood, but in a few cases it is empty and contracted.

In a case which Schauenstein has recorded[439] he found strychnine still

undissolved, coating the stomach as a white powder; but this is very

unusual, and I believe unique. The bladder often contains urine, which,

it need scarcely be said, should be preserved for chemical

investigation.

[439] _Op. cit._

§ 396. =Treatment.=--From the cases detailed, and from the experiments

on animals, the direction which treatment should take is very clear. As

a matter of course, if there is the slightest probability of any of the

poison remaining in the stomach, it should be removed. It is doubtful

whether the stomach pump can be ever applied with benefit in strychnine

poisoning, the introduction of the tube is likely to aggravate the

tetanus, but apomorphine can be injected subcutaneously. Large and

frequent doses of chloral should be administered in order to lessen the

frequency of convulsions, or prevent their occurrence, and it may be

necessary in a few cases, where death threatens by suffocation, to

perform tracheotomy, and to use artificial respiration. Where chloral or

chloroform is not at hand, and in cases of emergency, where this may

easily happen, the medical man must administer in full doses the nearest

narcotic at hand.[440]

[440] It is certain that lutidine would be a valuable antidote for

strychnine. C. G. Williams found that lutidine injected into frogs

already under the influence of strychnine, arrested the convulsions, or

if given first, and then followed by a fatal dose of strychnine, it

prevented the appearance of the tetanus. (See _ante_, p. 276, footnote.)

§ 397. =Separation of Strychnine from Organic Matters.=--The separation

of strychnine from organic matters, &c., is undertaken strictly on the

general principles already detailed. It may happen, however, that in

cases of poisoning there is the strongest evidence from symptoms in the

person or animal that strychnine alone is to be sought for. In an

instance of the kind, if a complex organic liquid (such as the contents

of the stomach) is under examination, it is best to remove the solid

substances by filtration through glass, wool, or linen, and evaporate

nearly to dryness over the water-bath, acidifying with acetic acid, and

then exhausting the residue repeatedly with boiling alcohol of 80 per

cent. The alcoholic extract is in its turn evaporated to dryness, and

taken up with water; the aqueous solution is passed through a wet

filter, and then shaken up with the usual succession of fluids, viz.,

petroleum ether, benzene, chloroform, and amyl alcohol, which will

remove a great number of impurities, but will not dissolve the

strychnine from the acid solution. The amyl alcohol may lastly be

removed by petroleum ether; and on removal of the final extractive

(which should be done as thoroughly as possible) chloroform is added,

and the fluid is alkalised by ammonia, which precipitates the alkaloid

in the presence of the solvent. Should the reverse process be

employed--that is, ammonia added first, and then chloroform--the

strychnine is not so perfectly dissolved, since it has time to assume a

crystalline condition. On separation and evaporation of the chloroform,

the residue (if much discoloured, or evidently impure) may be dissolved

in alcohol or benzene, and recrystallised several times. Cushman has

published an improved method of separating strychnine, which, according

to test experiments, appears to give good results. He describes the

method as follows:[441]--

[441] “The _post-mortem_ Detection and Estimation of Strychnine,” by

Allerton S. Cushman--_Chem. News_, vol. lxx. 28.

“The stomach contents or viscera properly comminuted are weighed,

and an aliquot part taken for analysis. The mass is digested in a

beaker over night, at a warm temperature, with water acidulated with

acetic acid. The contents of the beaker are filtered by pressing

through muslin, and then passing through paper. The clear filtrate

is evaporated on the water-bath to soft dryness, an excess of

ordinary 80 per cent. alcohol added, and boiled ten minutes with

stirring, and allowed to stand one half hour at a warm temperature.

This extraction is repeated, the alcohol extracts united, filtered,

evaporated to soft dryness, and the residue taken up with a little

water acidulated with acetic acid, and shaken out with pure acetic

ether in a separating funnel. Successive fresh portions of acetic

ether are used until the solvent shows by its colour, and by the

evaporation of a few drops, that it does not contain extractive

matter. As many as twelve extractions are sometimes necessary to

accomplish this. Care should be taken in each case to allow time for

as complete separation as possible between the two layers. The

purified acid aqueous liquid, which need not exceed in bulk 50 c.c.,

is now returned to the separator, an equal quantity of fresh acetic

ether added, and enough sodic carbonate in solution to render the

mixture slightly alkaline, and the separator is then thoroughly

shaken for several minutes. All the alkaloid should now be in

solution in the acetic ether, but a second shaking of the alkaline

liquid, with acetic ether, is always made, the two extracts united,

and evaporated in a glass dish over hot water to dryness. It will

now be found that the residue shows the alkaloid fairly pure, but

not pure enough for quantitative results. The residue is dissolved

in a few drops of dilute acetic acid, warmed to complete solution,

filtered if necessary, diluted to about 30 c.c., and the solution

transferred to a small separating funnel; 30 c.c. of

ether-chloroform (1-1) are now added, and the separator shaken.

After separation the heavier ether-chloroform is allowed to run off,

another lot of 30 c.c. of ether-chloroform is added, the separator

shaken, and immediately enough ammonia-water added to render the

mixture alkaline, and the whole vigorously agitated for several

minutes. After separation is complete, the ether-chloroform layer is

run out into a clean 50 c.c. glass-stoppered burette. The alkaline

water solution is agitated with 20 c.c. more of the

ether-chloroform, separated, and this extract added to that in the

burette. The burette is now supported over a small weighed glass

dish, which is kept warm on a water-bath, and the liquid allowed to

evaporate gently, drop by drop, until a sufficient quantity of the

pure alkaloid has collected in the centre of the dish to render an

accurate weighing possible, or else all of the alkaloid may be

collected and weighed at once. After all possible tests have been

made upon the weighed alkaloid, the remainder is re-dissolved in a

drop or two of acetic acid, a little water added, and the dish

exposed under a bell-glass to the fumes of ammonia. After standing

some time all the strychnine is found crystallised out in the

beautiful characteristic needle-formed crystals. The mother-liquor

is drawn off with a small fine-pointed tube and rubber bulb, the

crystals carefully washed with a little water and dried over

sulphuric acid. The glass dish containing these crystals is kept as

the final exhibit, and is shown in evidence. Another convenient

exhibit may be prepared by moistening a small filter-paper with a

solution of the alkaloid in dilute acetic acid, then moistening with

a solution of potassium dichromate: this paper, on being dried, may

be kept indefinitely. On moistening it, and touching it at any time

with a drop of strong sulphuric acid, a violet film, changing to

cherry-red, is formed at the place of contact.”

Should search be made for minute portions of strychnine in the tissues,

considering the small amount of the poison which may produce death, it

is absolutely necessary to operate on a very large quantity of material.

It would be advisable to take the whole of the liver, the brain, spinal

cord, spleen, stomach, duodenum, kidneys, all the blood that can be

obtained, and a considerable quantity of muscular tissue, so as to make

in all about one-eighth to one-tenth of the whole body; this may be cut

up into small pieces, and boiled in capacious flasks with alcohol,

acidified with acetic acid. Evaporation must be controlled by adapting

to the cork an upright condenser.

Should the analyst not have apparatus of a size to undertake this at

one operation, it may be done in separate portions--the filtrate from

any single operation being collected in a flask, and the spirit

distilled off in order to be used for the next. In this way, a large

quantity of the organs and tissues can be exhausted by half a gallon of

alcohol. Finally, most of the alcohol is distilled off, and the

remainder evaporated at a gentle heat in a capacious dish, the final

extract being treated, evaporating to a syrup, and using Cushman’s

process (_ante_, p. 334) as just described. It is only by working on

this large scale that there is any probability of detecting absorbed

strychnine in those cases where only one or two grains have destroyed

life, and even then it is possible to miss the poison.

Strychnine is separated by the kidneys rapidly. In a suicidal case

recorded by Schauenstein,[442] death took place in an hour and a half

after taking strychnine, yet from 200 c.c. of the urine, Schauenstein

was able to separate nitrate of strychnine in well-formed crystals. Dr.

Kratter[443] has made some special researches on the times within which

strychnine is excreted by the kidneys. In two patients, who were being

treated by subcutaneous injection, half an hour after the injection of

7·5 mgrms. of strychnine nitrate the alkaloid was recognised in the

urine. The strychnine treatment was continued for eight to ten days, and

then stopped; two days after the cessation, strychnine was found in the

urine, but none on the third day, and the inference drawn is that the

elimination was complete within forty-eight hours.

[442] Maschka’s _Handbuch_, Band 2, p. 620.

[443] _Ibid._

Strychnine has been detected in the blood of dogs and cats in researches

specially undertaken for that purpose, but sometimes a negative result

has been obtained, without apparent cause. Dragendorff[444] gave dogs

the largest possible dose of strychnine daily. On the first few days no

strychnine was found in the urine, but later it was detected, especially

if food was withheld. M’Adam was the first who detected the absorbed

poison, recognising it in the muscles and urine of a poisoned horse, and

also in the urine of a hound. Dragendorff has found it in traces in the

kidneys, spleen, and pancreas; Gay, in different parts of the central

nervous system, and in the saliva. So far as the evidence goes, the

liver is the best organ to examine for strychnine; but all parts

supplied with blood, and most secretions, may contain small quantities

of the alkaloid. At one time it was believed that strychnine might be

destroyed by putrefaction, but the question of the decomposition of the

poison in putrid bodies may be said to be settled. So far as all

evidence goes, strychnine is an extremely stable substance, and no

amount of putrescence will destroy it. M’Adam found it in a horse a

month after death, and in a duck eight weeks after; Nunneley in 15

animals forty-three days after death, when the bodies were much

decomposed; Roger in a body after five weeks’ interment; Richter in

putrid tissues exposed for eleven years to decomposition in open

vessels; and, lastly, W. A. Noyes[445] in an exhumed body after it had

been buried 308 days.

[444] In an animal rapidly killed by a subcutaneous injection of acetate

of strychnine, no strychnine was detected either in the blood or

liver.--_Dragendorff._

[445] _Journ. Americ. Chem. Soc._, xvi. 2.

It would appear from Ibsen’s[446] experiments that strychnine gets

dissolved in the fluids of the dead body--so that whether strychnine

remains or not, greatly depends as to whether the fluids are retained or

are allowed to soak away; it is, therefore, most important in

exhumations to save as much of the fluid as possible.

[446] _Viertel. f. gericht. Med._, Bd. viii.

§ 398. =Identification of the Alkaloid.=--A residue containing

strychnine, or strychnine mixed with brucine, is identified--

(1.) By its alkaline reaction and its bitter taste. No substance can

possibly be strychnine unless it tastes remarkably bitter.

(2.) By the extremely insoluble chromate of strychnine, already

described.[447] A fluid containing 1 : 1000 of strychnine gives with

chromate of potash (if allowed to stand over-night) a marked

precipitate, dissimilar to all others, except those of lead and baryta

chromates, neither of which can possibly occur if any of the processes

described are followed.

[447] 1 grm. of strychnine gave 1·280 grms. of the chromate, = 78·1 per

cent. of strychnine; 3 gave 3·811 of the chromate, = 78·77 per cent. of

strychnine.--_Mohr._

(3.) If the chromate just described is treated on a porcelain plate with

a drop of pure strong sulphuric acid, a deep rich blue colour, passing

through purple into red, rapidly makes its appearance. This colour

possesses an absorption spectrum (figured at p. 55). Dr. Guy, neglecting

intermediate colours, aptly compares the succession--(1) to the rich

blue of the Orleans plum; (2) to the darker purple of the mulberry; and

(3) to the bright clear red of the sweet orange. These characters--viz.,

alkalinity, bitterness, and the property of precipitation by potassic

chromate in a definite crystalline form, the crystals giving the

colours detailed--belong to no other substance known save strychnine,

and for all purposes sufficiently identify the alkaloid. The same

colour is obtained by mixing a drop of sulphuric acid with

strychnine and a crystal, or speck, of any one of the following

substances:--Ferridcyanide of potash, permanganate of potash, peroxide

of lead, peroxide of manganese, and cerous hydroxide.

Potassic permanganate and sulphuric acid is the most delicate, and will

detect 0·001 mgrm. of strychnine; cerous hydroxide is, on the other

hand, most convenient, for cerous hydroxide is white; all the others

have colours of their own. Cerous hydroxide is prepared strychnine; 3

gave 3·811 of the chromate, = 78·77 per cent. of strychnine.--_Mohr._

by dissolving cerium oxalate in dilute sulphuric acid and precipitating

with ammonia, filtering and well washing the precipitate; and the latter

may be used while moist, and responds well to 1/100 mgrm. of strychnine.

The influence of mixtures on the colour reactions of strychnine have

been studied by Flückiger, who states:--

“No strychnine reaction appears with sulphuric acid containing chromic

acid (made by dissolving 0·02 grm. of pot. bichromate in 10 c.c. of

water, and then adding 30 grms. strong sulphuric acid) when brucine and

strychnine mixed in equal parts are submitted to the test; it succeeds,

however, in this proportion with sulphuric acid containing potassium

permanganate (·02 grm. pot. permanganate in 10 c.c. of water, and 30

grms. of strong sulphuric acid).

“If the brucine is only one-tenth of the mixture, the blue-violet colour

is obtained. A large excess of atropine does not prevent or obscure the

strychnine reaction. A solution of 1 milligrm. atropine sulphate

evaporated to dryness, together with 5 c.c. of a solution of strychnine

(1 : 100,000) has no influence on the reaction, neither in the

proportion of 1 mgrm. to 1 c.c. of the same solution; neither has

cinchonine nor quinine any effect.

“Morphine obscures the reaction in the following proportions:--

“A solution of 0·01 mgrm. strychnine evaporated with a solution of 1

mgrm. of morphine sulphate on a water-bath, yields a blurred strychnine

reaction when the residue is dissolved in sulphuric acid, and a crystal

of potassic permanganate added. But still there is evidence whereby to

_suspect_ the presence of strychnine.

“A solution of 2 mgrms. of morphine sulphate treated in like manner with

0·01 mgrm. of strychnine yields like results.

“A solution of 3 mgrms. of morphine sulphate evaporated to dryness, with

a solution of 0·01 mgrm. strychnine yielded results with the potassic

permanganate test the same as if no strychnine was present.

“A solution of 1 mgrm. of morphine sulphate, treated as above, with a

solution of 0·1 mgrm. strychnine, offered positive proof of the presence

of the latter.”[448]

[448] Flückiger’s _Reactions_, translated by Nagelvoort, Detroit, 1893.

Dragendorff was able to render evident ·025 mgrm. mixed with twenty

times its weight of quin. sulphate; the same observer likewise

recognised ·04 mgrm. of strychnine in thirty-three times its weight of

caffeine. Veratrine is likewise not injurious.

=The physiological test= consists in administering the substance to some

small animal (preferably to a frog), and inducing the ordinary tetanic

symptoms. It may be at once observed that if definite chemical evidence

of strychnine has been obtained, the physiological test is quite

unnecessary; and, on the other hand, should the application of a liquid

or substance to a frog induce tetanus, while chemical evidence of the

presence of strychnine was wanting, it would be hazardous to assert that

strychnine was present, seeing that caffeine, carbolic acid, picrotoxin,

certain of the opium alkaloids, hypaphorine, some of the ptomaines, and

many other substances induce similar symptoms. The best method (if the

test is used at all) is to take two frogs,[449] and insert under the

skin of the one the needle of a subcutaneous syringe, previously charged

with a solution of the substance, injecting a moderate quantity. The

other frog is treated similarly with a very dilute solution of

strychnine, and the two are then placed under small glass shades, and

the symptoms observed and compared. It is not absolutely necessary to

inject the solution under the skin, for if applied to the surface the

same effects are produced; but, if accustomed to manipulation, the

operator will find the subcutaneous application more certain, especially

in dealing with minute quantities of the alkaloid.[450]

[449] A very practical disadvantage of the physiological test is the

great difficulty of obtaining frogs exactly when wanted.

[450] Methyl strychnine, as well as methyl brucine, has been shown by

Brown and Fraser to have an effect exactly the opposite to that of

strychnine, paralysing the muscles like curare. In the case, therefore,

of the methyl compounds, a physiological test would be very valuable,

since these compounds do not respond to the ordinary tests.

§ 399. =Hypaphorine.=--One substance is known which neither

physiological test nor the colour reactions suffice to distinguish

from strychnine, viz., hypaphorine,[451] the active matter of a

papilionaceous tree growing in Java--the _Hypaphorus subumbrans_; a

small quantity of the alkaloid is in the bark, a larger quantity is

in the seed.

[451] Dr. C. Plugge, _Arch. f. exp. Path. u. Ph._, Bd. xxxii. 313.

Hypaphorine forms colourless crystals which brown, without melting,

above 220°, and exhale a vapour smelling like napththylamine. The

free alkaloid is soluble in water, but has no action on litmus. The

salts are less soluble than the free alkaloid, so that acids, such

as nitric or hydrochloric, produce in a short time precipitates on

standing. Solutions of the salts are not precipitated by alkalies;

chloroform, ether, benzene, all fail to extract it from either

alkaline or acid solutions. It gives no precipitate with potassic

chromate, but most general alkaloidal reagents precipitate.

It gives a precipitate with iodine trichloride, and has therefore

probably a pyridine nucleus, it may be an acid anilide.[452] It

gives the same colours as strychnine with sulphuric acid and

potassic permanganate or potassic chromate; it causes in frogs

tetanus, but the dose has to be much larger than that of strychnine.

The duration of life in doses of 15 mgrms. may extend to five days,

and frogs may even recover after 50 mgrms.

[452] Julius Tafel (_Ber._, 1890, 412) has shown that the colour

reactions with H₂SO₄ and oxidising agents are the characteristic tests

of an acid anilide.

The distinction between strychnine and hypaphorine is therefore

easy; besides it will not occur in a chloroform extract, and it will

not give a precipitate with potassic chromate.

§ 400. =Quantitative Estimation of Strychnine.=--The best process of

estimating the proportion of each alkaloid in a mixture of

strychnine and brucine, is to precipitate them as picrates, and to

destroy the brucine picrate by nitric acid after obtaining the

combined weight of the mixed picrates; then to weigh the undestroyed

strychnine picrate.

To carry out the process, the solution of the mixed alkaloids must

be as neutral as possible. A saturated solution of picric acid is

added drop by drop to complete precipitation. A filter paper is

dried and weighed, and the precipitate collected on to this filter

paper; the precipitate is washed with cold water, dried at 105°, and

weighed. This weight gives the combined weight of both strychnine

and brucine picrates.

The precipitate is now detached from the filter, washed into a small

flask, and heated on the water-bath for some time with nitric acid

diluted to 1·056 gravity (about 11 per cent. HNO₃). This process

destroys the brucine picrate, but leaves the strychnine picrate

untouched. The acid liquid is now neutralised with ammonia or soda,

and a trace of acetic acid added; the precipitate of strychnine

picrate is now collected and weighed. The weight of this subtracted

from the first weight, of course, gives that of the brucine picrate.

One part of strychnine picrate is equal to 0·5932 strychnine; and

one part of brucine picrate is equal to 0·6324 brucine.

From the strychnine picrate the picric acid may be recovered and

weighed by dissolving the picrate in a mineral acid and shaking out

with ether; from the acid liquid thus deprived of picric acid the

alkaloid may be separated by alkalising with ammonia and shaking out

with chloroform.

§ 401. =Brucine= (C₂₃H₂₆N₂O₄ + 4H₂O)[453] occurs associated with

strychnine in the plants already mentioned; its best source is the

so-called _false angustura_ bark, which contains but little strychnine.

Its action is similar to that of strychnine. If crystallised out of

dilute alcohol it contains 4 atoms of water, easily expelled either in a

vacuum over sulphuric acid or by heat. Crystallised thus, it forms

transparent four-sided prisms, or arborescent forms, like boric acid. If

thrown down by ammonia from a solution of the acetate, it presents

itself in needles or in tufts.

[453] Sonnenschein has asserted that brucine may be changed into

strychnine by the action of NO₃. This statement has been investigated by

A. J. Cownley, but not confirmed.--_Pharm. Journ._ (3), vi. p. 841.

The recently-crystallised alkaloid has a solubility different from that

which has effloresced, the former dissolving in 320 parts of cold, and

150 parts of boiling water; whilst the latter (according to Pelletier

and Caventou) requires 500 of boiling, and 850 parts of cold water for

solution. Brucine is easily soluble in absolute, as well as in ordinary

alcohol; 1 part dissolves in 1·7 of chloroform, in 60·2 of benzene.

Petroleum ether, the volatile and fatty oils and glycerine, dissolve the

alkaloid slightly, amyl alcohol freely; it is insoluble in _anhydrous_

ether. The behaviour of brucine in the subliming cell is described at p.

260. Anhydrous brucine melts in a tube at 178°. The alcoholic solution

of brucine turns the plane of polarisation to the left [α]_r_ = -11·27°.

The taste is bitter and acrid. Soubeiran maintains that it can be

recognised if 1 part is dissolved in 500,000 parts of water. If nitric

trioxide be passed into an alcoholic solution of brucine, first brucine

nitrate is formed; but this passes again into solution, from which,

after a time, a heavy, granular, blood-red precipitate separates: it

consists of dinitro-brucine (C₂₃H₂₄(NO₂)₂N₂O₄). Brucine fully

neutralises acids, and forms salts, which are for the most part

crystalline. The neutral sulphate (C₂₃H₂₅N₂O₄SH₂O₄ + 3½H₂O) is in long

needles, easily soluble in water. The acetate is not crystalline, that

of strychnine is so (p. 321).

Brucine is precipitated by ammonia, by the caustic and carbonated

alkalies, and by most of the group reagents. Ammonia does not

precipitate brucine, if in excess; on the other hand, strychnine comes

down if excess of ammonia is added immediately. This has been proposed

as a method of separation; if the two alkaloids are present in acid

solution, ammonia in excess is added, and the solution is immediately

filtered; the quantitative results are, however, not good, the

strychnine precipitate being invariably contaminated by brucine.

Chromate and dichromate of potassium give no precipitate with neutral

salts of brucine; on the other hand, strychnine chromate is at once

formed if present. It might, therefore, be used to separate strychnine

from brucine. The author has attempted this method, but the results were

not satisfactory.

§ 402. =Physiological Action.=--The difference between the action of

strychnine and that of brucine on man or animals is not great. Mays

states that strychnine affects more the anterior, brucine the posterior

extremities. In strychnine poisoning, convulsions occur early, and

invariably take place before death; but death may occur from brucine

without any convulsions, and in any case they develop late. Brucine

diminishes local sensibility when applied to the skin; strychnine does

not.[454] In a physiological sense, brucine may be considered a diluted

strychnine. The lethality of brucine, especially as compared with

strychnine, has been investigated by F. A. Falck.[455] He experimented

on 11 rabbits, injecting subcutaneously brucine nitrate, in doses of

varying magnitude, from 100 mgrms. down to 20 mgrms. per kilogram of

body-weight. He found that brucine presented three stages of symptoms.

In the first, the respiration is quickened; in 3 of the 11 cases a

strange injection of the ear was noticed; during this period the pupils

may be dilated. In the second stage, there are tetanic convulsions,

trismus, opisthotonus, oppressed respiration, and dilated pupils. In the

third stage, the animal is moribund. Falck puts the minimum lethal dose

for rabbits at 23 mgrms. per kilo. Strychnine kills 3·06 times more

quickly than brucine, the intensity of the action of strychnine relative

to that of brucine being as 1 : 117·4. Falck has also compared the

minimum lethal dose of strychnine and brucine with the tetanising opium

alkaloids, as shown in the following table:--

[454] _Journ. Physiol._, viii. 391-403.

[455] _Brucin u. Strychnin; eine toxikologische Parallele_, von Dr. F.

A. Falck. _Vierteljahrsschr. f. gerichtl. Med._, Band xxiii. p. 78.

TABLE SHOWING THE LETHAL DOSES OF VARIOUS TETANISING POISONS.

+-----------------------+---------------+------------+

| |Minimum Lethal | |

| |Dose for every |Proportional|

| |Kilogram Weight| Strength. |

| | of Rabbit. | |

+-----------------------+---------------+------------+

| | Mgrms. | |

| | | |

|Strychnine nitrate, | 0·6 | ... |

|Thebaine nitrate, | 14·4 | 24·0 |

|Brucine nitrate, | 23·0 | 38·33 |

|Landanine nitrate, | 29·6 | 49·33 |

|Codeine nitrate, | 51·2 | 85·33 |

|Hydrocotarnine nitrate,| 203·8 | 339·66 |

+-----------------------+---------------+------------+

If these views are correct, it follows that the least fatal dose for an

adult man would be 1·64 grm. (about 24·6 grains) of brucine nitrate.

[Illustration: Brucine Crystals. (_From a Photograph._)]

§ 403. Tests.--If to a solution of brucine in strong alcohol a little

methyl iodide is added, at the end of a few minutes circular rosettes of

crystal groups appear (see fig.): they are composed of methyl brucine

iodide (C₂₃H₂₅(CH₃)N₂O₄HI). Crystals identical in shape are also

obtained if an alcoholic solution of iodine, or hydriodic acid with

iodine, is added to an alcoholic solution of brucine. A solution of

strychnine gives with methyl iodide no similar reaction. Strychnine in

alcoholic solution, mixed with, brucine in no way interferes with the

test. The methyl iodide test may be confirmed by the action of nitric

acid. With that reagent it produces a scarlet colour, passing into

blood-red, into yellow-red, and finally ending in yellow. This can be

made something more than a mere colour test, for it is possible to

obtain a crystalline body from the action of nitric acid on brucine. If

a little of the latter be put in a test-tube, and treated with nitric

acid of 1·4 specific gravity (immersing the test-tube in cold water to

moderate the action), the red colour is produced. On spectroscopic

examination of the blood-red liquid a broad, well-marked absorption band

is seen, the centre of which (_see_ page 55) is between E. & F. [W. L.

about 500]. There is also a development of nitric oxide and carbon

dioxide, and the formation of methyl nitrite, oxalic acid, and kakotelin

(C₂₃H₂₆N₂O₄ + 5NHO₃ = C₂₀H₂₂N₄O₉ + N(CH₃)O₂ + C₂H₂O₄ + 2NO + 2H₂O). On

diluting abundantly with water, the kakotelin separates in yellow

flocks, and may be crystallised out of dilute hydrochloric or dilute

nitric acid in the form of yellow or orange-red crystals, very insoluble

in water, but dissolving readily in dilute acid. On removal by dilution

of the product just named, neutralisation with ammonia, and addition of

a solution of chloride of calcium, the oxalate of lime is thrown down.

The nitric acid test is, therefore, a combined test, consisting of--the

production by the action of nitric acid (1) of a red colour; (2) of

yellow scales or crystals insoluble in water; (3) of oxalic acid. No

alkaloid save brucine is known to give this reaction.

There are other methods of producing the colour test. If a few drops of

nitric acid are mixed with the substance in a test-tube, and then

sulphuric acid cautiously added, so as to form a layer at the bottom, at

the junction of the liquids a red zone, passing into yellow, is seen.

A solution of brucine is also coloured red by chlorine gas, ammonia

changing the colour into yellow.

Flückiger[456] has proposed as a test mercurous nitrate, in aqueous

solution with a little free nitric acid. On adding this reagent to a

solution of brucine salt, and gently warming, a fine carmine colour is

developed.

[456] _Archiv f. Pharm._ (3), vi. 404.

In regard to the separation of brucine from organic fluids or tissues,

the process already detailed for strychnine suffices. It is of very

great importance to ascertain whether both strychnine and brucine are

present or not--the presence of both pointing to nux vomica or one of

its preparations. The presence of brucine may, of course, be owing to

impure strychnine; but if found in the tissues, that solution of the

question is improbable, the commercial strychnine of the present day

being usually pure, or at the most containing so small a quantity of

brucine as would hardly be separated from the tissues.

§ 404. =Igasurine= is an alkaloid as yet but little studied; it

appears that it can be obtained from the boiling-hot watery extract

of nux vomica seeds, through precipitating the strychnine and

brucine by lime, and evaporation of the filtrate. According to

Desnoix,[457] it forms white crystals containing 10 per cent. of

water of crystallisation.

[457] _Journ. Pharm._ (3), xxv. 202.

It is said to be poisonous, its action being similar to that of

strychnine and brucine, and in activity standing midway between the

two.

§ 405. _Strychnic Acid._--Pelletier and Caventou obtained by boiling

with spirit small, hard, warty crystals of an organic acid, from _S.

ignatius_, as well as from nux vomica seeds. The seeds were first

exhausted by ether, the alcohol solution was filtered and

evaporated, and the extract treated with water and magnesia,

filtered, and the residue first washed with cold water, then with

hot spirit, and boiled lastly with a considerable quantity of water.

The solution thus obtained was precipitated with acetate of lead,

the lead thrown out by SH₂, and the solution evaporated, the acid

crystallising out. It is a substance as yet imperfectly studied, and

probably identical with malic acid.

2. THE QUEBRACHO GROUP OF ALKALOIDS.

§ 406. The bark of the _Quebracho Blanco_[458] (_Aspidosperma

quebracho_) contains, according to Hesse’s researches, no fewer than

six alkaloids--Quebrachine, Aspidospermine, Aspidospermatine,

Aspidosamine, and Hypoquebrachine. The more important of these are

_Aspidospermine_ and _Quebrachine_.

[458] See Liebig’s _Annal._, 211, 249-282; _Ber. der deutsch. Chem.

Gesellsch._, 11, 2189; 12, 1560.

=Aspidospermine= (C₂₂H₃₀N₂O₂) forms colourless needles which melt at

206°. They dissolve in about 6000 parts of water at 14°--48 parts of

90 per cent. alcohol, and 106 parts of pure ether. The alkaloid

gives a fine magenta colour with perchloric acid.

=Quebrachine= (C₂₁H₂₆N₂O₃) crystallises in colourless needles,

melting-point (with partial decomposition) 215°. The crystals are

soluble in chloroform, with difficulty soluble in cold alcohol, but

easily in hot. The alkaloid, treated with sulphuric acid, and

peroxide of lead, strikes a beautiful blue colour. It also gives

with sulphuric acid and potassic chromate the strychnine colours.

Quebrachine, dissolved in sulphuric acid containing iron, becomes

violet-blue, passing into brown. The alkaloid, treated with strong

sulphuric acid, becomes brown; on adding a crystal of potassic

nitrate, a blue colour is developed; on now neutralising with

caustic soda no red coloration is perceived. Dragendorff has

recently studied the best method of extracting these alkaloids for

toxicological purposes. He recommends extraction of the substances

with sulphuric acid holding water, and shaking up with solvents.

Aspidospermine is not extracted by petroleum ether or benzene from

an acid watery extract, but readily by chloroform or by amyl

alcohol. It is also separated from the same solution, alkalised by

ammonia, by either amyl alcohol or chloroform; with difficulty by

petroleum ether; some is dissolved by benzene. Quebrachine may be

extracted from an acid solution by chloroform, but not by petroleum

ether. Alkalised by ammonia, it dissolves freely in chloroform and

in amyl alcohol. Traces are taken up by petroleum, somewhat more by

benzene. Aspidospermine is gradually decomposed in the body, but

Quebrachine is more resistant, and has been found in the stomach,

intestines, blood, and urine. The toxicological action of the bark

ranks it with the tetanic class of poisons. In this country it does

not seem likely to attain any importance as a poison.

3. PEREIRINE.

§ 407. =Pereirine=--an alkaloid from pereira bark--gives a play of

colours with sulphuric acid and potassic bichromate similar to but

not identical with that of strychnine. Fröhde’s reagent strikes

with it a blue colour. On dissolving pereirine in dilute sulphuric

acid, and precipitating by gold chloride, the precipitate is a

beautiful red, which, on standing and warming, is deepened.

Pereirine may be extracted from an acid solution, after alkalising

with ammonia, by ether or benzene.

4. GELSEMINE.

§ 408. Gelsemine (C₂₂H₂₈N₂O₄) is an alkaloid[459] which has been

separated from _Gelsemium sempervirens_, the Carolina jessamine, a

plant having affinities with several natural orders, and placed by

De Candolle among the _Loganiaceæ_, by Chapman among the _Rubiaceæ_

and by Decaisne among the _Apocynaceæ_. It grows wild in Virginia

and Florida.[460] Gelsemine is a strong base; it is yellowish when

impure, but a white amorphous powder when pure. It fuses below 100°

into a transparent vitreous mass, at higher temperatures it

condenses on glass in minute drops; its taste is extremely bitter;

it is soluble in 25 parts of ether, in chloroform, bisulphide of

carbon, benzene, and in turpentine; it is not very soluble in

alcohol, and still less soluble in water, but it freely dissolves in

acidulated water. The caustic alkalies precipitate it, the

precipitate being insoluble in excess; it is first white, but

afterwards brick-red. Tannin, picric acid, iodised potassic iodide,

platinic chloride, potassio-mercuric iodide, and mercuric chloride

all give precipitates. Fröhde’s reagent gives with gelsemine a brown

changing to green.

[459] Dr. T. G. Wormley separated, in 1870, a non-nitrogenised

remarkably fluorescent body, which he named gelsemic acid (_Amer. Journ.

of Pharm._, 1870), but Sonnenschein and C. Robbins afterwards found

gelsemic acid to be identical with æsculin (_Ber. der deutsch. Chem.

Ges._, 1876, 1182). Dr. Wormley has, however, contested this, stating

that there are differences. (_Amer. Journ. of Pharm._, 1882, p. 337.

_Yearbook of Pharmacy_, 1882, p. 169.)

[460] The following are its botanical characters:--Calyx five-parted,

corolla funnel-shaped, five-lobed, somewhat oblique, the lobes almost

equal, the posterior being innermost in bud; stamens five; anthers

oblong sagittate, style long and slender; stigmas two, each two-parted,

the divisions being linear; fruit elliptical, flattened contrary to the

narrow partition, two-celled, septicidally two-valved, the valves

keeled; seeds five to six in each cell, large, flat, and winged; embryo

straight in fleshy albumen; the ovate flat, cotyledons much shorter than

the slender radicle; stem smooth, twining and shrubby; leaves opposite,

entire, ovate, or lanceolate, shining on short petioles, nearly

persistent; flowers large, showy, very fragrant, yellow, one to five in

the axil of the leaves.

Sulphuric acid dissolves gelsemine with a reddish or brownish

colour; after a time it assumes a pinkish hue, and if warmed on the

water-bath, a more or less purple colour; if a small crystal of

potassic bichromate be slowly stirred in the sulphuric acid

solution, reddish purple streaks are produced along the path of the

crystal; ceric oxide exhibits this better and more promptly, so

small a quantity as ·001 grain showing the reaction. This reaction

is something like that of strychnine, but nitric acid causes

gelsemine to assume a brownish-green, quickly changing to a deep

green--a reaction which readily distinguishes gelsemine from

strychnine and other alkaloids.

§ 409. =Fatal Dose.=--10 mgrms. killed a frog within four hours, and

8 mgrms. a cat within fifteen minutes. A healthy woman took an

amount of concentrated tincture, which was equivalent to 11 mgrms.

(⅙ grain), and died in seven and a half hours.

§ 410. =Effects on Animals--Physiological Action.=--Gelsemine acts

powerfully on the respiration; for example, Drs. Sydney Ringer and

Murrell[461] found, on operating on the frog, that in two minutes

the breathing had become distinctly slower; in three and a half

minutes, it had been reduced by one-third; and in six minutes, by

one-half; at the expiration of a quarter of an hour, it was only

one-third of its original frequency; and in twenty minutes, it was

so shallow and irregular that it could no longer be counted with

accuracy. In all their experiments they found that the respiratory

function was abolished before reflex and voluntary motion had become

extinct. In several instances the animals could withdraw their legs

when their toes were pinched, days after the most careful

observations had failed to detect the existence of any respiratory

movement. The heart was seen beating through the chest wall long

after the complete abolition of respiration.

[461] _Lancet_, vol. i., 1876, p. 415.

In their experiments on warm-blooded animals (cats), they noticed

that in a few minutes the respirations were slowed down to 12 and

even to 8, and there was loss of power of the posterior extremities,

while at short intervals the upper half of the body was convulsed.

In about half an hour paralysis of the hind limbs was almost

complete, and the respiratory movements so shallow that they could

not be counted. In the case of a dog, after all respiration had

ceased tracheotomy was performed, and air pumped in: the animal

recovered.

Ringer and Murrell consider that gelsemine produces no primary

quickening of the respiration, that it has no direct action on

either the diaphragm or intercostal muscles, that it paralyses

neither the phrenic nor the intercostal nerves, and that it

diminishes the rate of respiration after both vagi have been

divided. They do not consider that gelsemine acts on the cord

through Setschenow’s inhibitory centre, but that it destroys reflex

power by its direct action on the cord, and that probably it has no

influence on the motor nerves. Dr. Burdon Sanderson has also

investigated the action of gelsemine on the respiration, more

especially in relation to the movements of the diaphragm. He

operated upon rabbits; the animal being narcotised by chloral, a

small spatula, shaped like a teaspoon, was introduced into the

peritoneal cavity through an opening in the linea alba, and passed

upwards in front of the liver until its convex surface rested

against the under side of the centrum tendineum. The stem of the

spatula was brought into connection with a lever, by means of which

its to-and-fro movements (and consequently that of the diaphragm)

were inscribed. The first effect is to augment the depth but not the

frequency of the respiratory movements; the next is to diminish the

action of the diaphragm both in extent and frequency. This happens

in accordance with the general principle applicable to most cases of

toxic action--viz., that paresis of a central organ is preceded by

over-action. The diminution of movement upon the whole is

progressive, but this progression is interrupted, because the blood

is becoming more and more venous, and, therefore, the phenomena of

asphyxia are mixed up with the toxical effects. Dr. Sanderson

concludes that the drug acts by paralysing the automatic respiratory

centre; the process of extinction, which might be otherwise expected

to be gradual and progressive, is prevented from being so by the

intervention of disturbances of which the explanation is to be found

in the imperfect arterialisation of the circulating blood. Ringer

and Murrell have also experimented upon the action of gelsemine on

the frog’s heart. In all cases it decreased the number of beats; a

small fatal dose produced a white contracted heart, a large fatal

dose, a dark dilated heart; in either case arrest of the circulation

of course followed.

§ 411. =Effects on Man.=--The preparations used in medicine are the

fluid extract and the tincture of gelsemine; the latter appears to

contain the resin of the root as well as the active principle. There

are several cases on record of gelsemine, or the plant itself,

having been taken with fatal effect.[462] Besides a marked effect on

the respiration, there is an effect upon the eye, better seen in man

than in the lower animals; the motor nerves of the eye are attacked

first, objects cannot be fixed, apparently dodging their position,

the eyelids become paralysed, droop, and cannot be raised by an

effort of the will; the pupils are largely dilated, and at the same

time a feeling of lightness has been complained of in the tongue; it

ascends gradually to the roof of the mouth, and the pronunciation is

slurred. There is some paresis of the extremities, and they refuse

to support the body; the respiration becomes laboured, and the pulse

rises in frequency to 120 or 130 beats per minute, but the mind

remains clear. The symptoms occur in about an hour and a half after

taking an overdose of the drug, and, if not excessive, soon

disappear, leaving no unpleasantness behind. If, on the other hand,

the case proceeds to a fatal end, the respiratory trouble increases,

and there may be convulsions, and a course very similar to that seen

in experimenting on animals. Large doses are especially likely to

produce tetanus, which presents some clinical differences

distinguishing it from strychnine tetanus. Gelsemine tetanus is

always preceded by a loss of voluntary reflex power, respiration

ceases before the onset of convulsions, the posterior extremities

are most affected, and irritation fails to excite another paroxysm

till the lapse of some seconds, as if the exhausted cord required

time to renew its energy; finally, the convulsions only last a short

time.

[462] See _Lancet_, 1873, vol. ii. p. 475; _Brit. Med. and Surg.

Journ._, April 1869; _Phil. Med. and Surg. Reporter_, 1861.

§ 412. _Extraction from Organic Matters, or the Tissues of the

Body._--Dragendorff states that, from as little as half a grain of

the root, both gelsemine and gelsemic acid may be extracted with

acid water, and identified. On extracting with water acidified with

sulphuric acid, and shaking up the acid liquid with chloroform, the

gelsemic acid (æsculin?) is dissolved, and the gelsemine left in the

liquid. The chloroform on evaporation leaves gelsemic acid in little

micro-crystals; it may be identified by (1) its crystallising in

little tufts of crystals; (2) its strong fluorescent properties, one

part dissolved in 15,000,000 parts of water showing a marked

fluorescence, which is increased by the addition of an alkali; and

(3) by splitting up into sugar and another body on boiling with a

mineral acid. After separation of gelsemic acid, the gelsemine is

obtained by alkalising the liquid, and shaking up with fresh

chloroform; on separation of the chloroform, gelsemine may be

identified by means of the reaction with nitric acid, and also the

reaction with potassic bichromate and sulphuric acid.

5. COCAINE.

§ 413. =Cocaine= (C₁₇H₂₁NO₄).--There are two cocaines--the one

rotating a ray of polarised light to the left, the other to the

right. The left cocaine is contained in the leaves of _Erythroxylon

coca_ with other alkaloids, and is in commerce.

Cocaine has been used most extensively in medicine since the year

1884--its chief use being as a local anæsthetic. Chemically cocaine

is a derivative of ecgonin, being ecgonin-methyl-ester. It has a

pyridine nucleus, and may be written

C₅H₄N(CH₃)--H₃CHO--(COC₆H₅)--CH₂COOCH₃, or expressed graphically as

follows:--

CH₂

CH / \CH₂

║ |

║Py | H

║ | /

CH \ /C--CHO(C₆H₅CO)--CH₂COOCH₃.

NCH₃

=Properties.=--Cocaine is in the form of four- to six-sided prisms

of the monoclinic system. It is one of the few alkaloids which melt

under the temperature of boiling water, the melting-point being as

low as 85° in water. It readily furnishes a sublimate at 100°,

partially decomposing. On boiling with hydrochloric acid cocaine is

decomposed into methyl alcohol, ecgonin, and benzoic acid, according

to the following reaction:--

Benzoic Methyl

Cocaine. acid. Ecgonin. Alcohol.

C₁₇H₂₁NO₄ + 2H₂O = C₆H₅COOH + C₉H₁₅NO₃ + CH₃OH.

Cocaine is but little soluble in water, but easily dissolves in

ether, alcohol, benzene, chloroform, and carbon disulphide; an

aqueous solution is alkaline to methyl-orange, but not to

phenol-phthalein. It can be made synthetically by the reaction of

ecgonin-methyl-ester with benzoyl chloride.

§ 414. =Cocaine Hydrochlorate= (C₁₇H₂₁NO₄HCl).--Crystallised from

alcohol, cocaine hydrochlorate appears in prismatic crystals; these

crystals, according to Hesse,[463] when perfectly pure, should melt at

186°, although the melting-point is generally given as 200° or even

202°. Cocaine hydrochlorate is soluble in half its weight of water,

insoluble in dry ether, but readily soluble in alcohol, amyl alcohol, or

chloroform.

[463] O. Hesse, _Annalen_, 276, 342-344.

§415. =Pharmaceutical Preparations.=--Cocaine hydrochlorate is

officinal. Gelatine discs, weighing 1·31 mgrms. (1/50 grain), and each

containing 0·33 mgrm. (1/200 grain) of the salt are officinal, and used

by ophthalmic surgeons. A solution of the hydrochlorate, containing 10

per cent. of cocaine hydrochlorate and (for the purposes of preserving

the solution) 0·15 per cent. of salicylic acid is also officinal.

Stronger solutions may also be met with; for instance, a 20 per cent.

solution in oil of cloves for external application in cases of

neuralgia.

§416. =Separation of Cocaine and Tests.=--Cocaine may be shaken out of

solutions made slightly alkaline by ammonia by treatment with benzene;

it also passes into petroleum ether under the same circumstances. The

best method is to extract a solution, made feebly alkaline, thoroughly

by ether, and then shake it out by benzene and evaporate the separated

benzene at the ordinary air temperature. The property of the alkaloid to

melt at or below the temperature of boiling water, and the ready

decomposition into benzoic acid and other products, render cocaine easy

of identification. If, for instance, a small particle of cocaine is put

in a tube, a drop of strong sulphuric acid added and warmed by the

water-bath, colourless crystals of benzoic acid sublime along the tube,

and an aromatic odour is produced.

Poisons, Their Effects and Detection A Manual for the Use of Analytical Chemists and Experts · 第 11 / 23 章

It therefore contains three methoxyl groups.