test both for cocaine and for cocaine hydrochlorate.
One drop of a dilute solution of ferric chloride added to a solution of
20 mgrms. of cocaine hydrochlorate in 2 c.c. of water, gives a yellow
fluid, which becomes red on boiling from the production of iron
benzoate. This reaction is of little use unless a solution of the same
strength of ferric chloride, but to which the substance to be tested has
not been added, is boiled at the same time for comparison, because all
solutions of ferric chloride deepen in colour on heating.
A solution of the alkaloid evaporated to dryness on the water-bath,
after being acidulated with nitric acid, and then a few drops of
alcoholic solution of potash or soda added, develops an odour of benzoic
ethyl-ester. Cocaine hydrochlorate, when triturated with calomel,
blackens by the slightest humidity or by moistening it with alcohol.
Cocaine in solution is precipitated by most of the group reagents, but
is not affected by mercuric chloride, picric acid, nor potassic
bichromate.
Added to the tests above mentioned, there is the physiological action;
cocaine dilates the pupil, tastes bitter, and, for the time, arrests
sensation; hence the after-effect on the tongue is a sensation of
numbness.
§ 417. =Symptoms.=--A large number of accidents occur each year from the
external application of cocaine; few, however, end fatally. Cocaine has
thus produced poisonous symptoms when applied to the eye, to the rectum,
to the gums, to the urethra, and to various other parts. There have been
a few fatal cases, both from its external and internal administration;
Mannheim, for example, has collected eleven of such instances.
The action of cocaine is twofold; there is an action on the central and
the peripheral nervous system. In small doses cocaine excites the spinal
cord and the brain; in large it may produce convulsions and then
paralysis. The peripheral action is seen in the numbing of sensation.
There is always interference with the accommodation of vision, and
dilatation of the pupil. The eyelids are wider apart than normal, and
there may be some protrusion of the eyeball.
The usual course of an acute case of poisoning is a feeling of dryness
in the nose and throat, difficulty of swallowing, faintness, and there
is often vomiting; the pulse is quickened; there is first cerebral
excitement, followed usually by great mental depression. Occasionally
there is an eruption on the skin. Hyperæsthesia of the skin is followed
by great diminution of sensation, the pupils, as before stated, are
dilated, the eyes protruding, the eyelids wide open, the face is pale,
and the perspiration profuse. Convulsions and paralysis may terminate
the scene. Death takes place from paralysis of the breathing centre;
therefore the heart beats after the cessation of respiration. As an
antidote, nitrite of amyl has apparently been used with success.
There is a form of chronic poisoning produced from the taking of small
doses of cocaine daily. The symptoms are very various, and are referable
to disturbance of the digestive organs, and to the effect on the nervous
system. The patients become extremely emaciated, and it seems to produce
a special form of mania.
§ 418. =Post-mortem Appearances.=--The appearances found in acute cases
of poisoning have been hyperæmia of the liver, spleen, and kidneys, as
well as of the brain and spinal cord.
In the experimental poisoning of mice with cocaine Ehrlich[464] found a
considerable enlargement of the liver.
[464] _Deutsche med. Wochens._, 1890, No. 32.
§ 419. =Fatal Dose.=--The fatal dose, according to Mannheim,[465] must
be considered as about 1 grm. (15·4 grains); the smallest dose known to
have been fatal is 0·08 grm. (1·2 grain) for an adult, and 0·05 grm.
(0·7 grain) for a child.
[465] _Deutsch. Arch. f. klin. Med._, Bd. viii., 1891, 380.
6. CORYDALINE.
§ 420. =Corydaline= (C₂₂H₂₈NO₄) is an alkaloid discovered by
Wackenroder (1826) in the tubers of _Corydalis tuberosa_;
crystallised in the cold and away from light, out of a mixture of
absolute alcohol and ether, corydaline forms colourless, flat,
prismatic crystals, which quickly turn yellow on exposure to light
or heat. Pure corydaline changes colour at about 125°, softens at
about 133°, and melts finally at 134° to 135°. It dissolves in
ether, chloroform, carbon disulphide, and benzene, but not so
readily in alcohol. It is almost insoluble in cold water, and but
slightly soluble in boiling water. Water precipitates it from a
solution in alcohol. It is also soluble in dilute hydrochloric and
sulphuric acids. It gives a precipitate with potassium iodide if a
solution of the hydrochloride be used. The precipitate crystallises
out of hot water in clusters of short lemon-yellow prismatic
crystals, and has the formula of C₂₂H₂₈NO₄HI. Corydaline
platinochloride has the composition of (C₂₂H₂₈NO₄)₂H₂PtCl₆,
containing Pt 16·94 per cent., and 2·44 per cent. of N.--Dobbie &
Lauder, _Journ. Chem. Soc._, March 1892, 244.
Corydaline in large doses causes epileptiform convulsions. Death
takes place from respiratory paralysis.
V.--The Aconite Group of Alkaloids.
§ 421. The officinal aconite is the _Aconitum napellus_--monkshood or
wolfsbane--a very common garden plant in this country, and one
cultivated for medicinal purposes. Many varieties of aconite exist in
other regions, which either are, or could be, imported. Of these the
most important is the _Aconitum ferox_, a native of the Himalayan
mountains, imported from India.
All the aconites, so far as known, are extremely poisonous, and it
appears probable that different species contain different alkaloids. The
root of _A. napellus_ is from 2 to 4 inches long, conical in shape,
brown externally, and white internally. The leaves are completely
divided at the base into five wedge-shaped lobes, each of the five lobes
being again divided into three linear segments. The numerous seeds are
three-sided, irregularly twisted, wrinkled, of a dark-brown colour, in
length one-sixth of an inch, and weighing 25 to the grain (_Guy_). The
whole plant is one of great beauty, from 2 to 6 feet high, and having a
terminal spike of conspicuous blue flowers. The root has been fatally
mistaken for horse-radish, an error not easily accounted for, since no
similarity exists between them.
§ 422. =Pharmaceutical Preparations of Aconite.=--The preparations of
aconite used in medicine are--
=Aconitine=, officinal in all the pharmacopœias.
=Aconite liniment= (=linimentum aconiti=), made from the root with
spirit, and flavoured with camphor; officinal in the British
Pharmacopœia. It may contain about 2·0 per cent. of aconitine.
=Aconite tincture=, officinal in all the pharmacopœias.
=Aconite ointment=, 8 grains of aconitine to the oz. (_i.e._, 1·66 per
cent.); officinal in the British Pharmacopœia.
=Aconite extract=, the juice of the leaves evaporated; officinal in most
of the pharmacopœias. The strength in alkaloid of the extract varies; in
six samples examined by F. Casson, the least quantity was 0·16 per
cent., the maximum 0·28 per cent.[466]
[466] _Pharm. Journ._, 1894, 901.
=Fleming’s tincture of aconite= is not officinal, but is sold largely in
commerce. It is from three to four times stronger than the B.P.
tincture.
§ 423. =The Alkaloids of Aconite.=--The researches of Dr. Alder Wright
and Luff, and especially those of Professor Dunstan,[467] have
established that in the root of the true aconite there exist four
alkaloids, one only of which has been as yet crystallised.
[467] Various papers in _Journ. Chem. Soc._, 1892-1894.
Three of the alkaloids have been fairly well worked out; the fourth
homo-napelline has not yet been satisfactorily investigated.
The three alkaloids are aconitine, aconine and benzoyl-aconine; besides
which pyraconitine and pyraconine can be obtained by suitable treatment
from aconitine and aconine.
The formulæ of the alkaloids and their derivatives are as follows:--
Aconitine (acetyl-benzoyl-aconine), m.p., 188·60°, C₃₃H₄₅NO₁₂
Benzoyl-aconine, m.p., 268·0°, C₃₁H₄₃NO₁₁
Pyraconitine (anhydro-benzoyl-aconine), m.p., 188-190°, C₃₁H₄₁NO₁₀
Aconine, m.p., 132°, C₂₄H₃₉NO₁₀
Pyraconine (anhydro-aconine), C₂₄H₃₇NO₉
§ 424. =Aconitine=, C₃₃H₄₅NO₁₂.--This base has been shown by Dunstan to
be acetyl-benzoyl-aconine; one molecule of the base breaking up, on
complete hydrolysis, into one molecule of aconine, one of acetic acid,
and one of benzoic acid--
Acetic Benzoic
Acid. Acid. Aconine.
C₃₃H₄₅NO₁₂ + 2H₂O = C₂H₄O₂ + C₇H₆O₂ + C₂₄H₃₉NO₁₀.
That is to say that 100 parts of aconitine, according to theory, should
yield:--
Acetic acid, 9·37 per cent.; benzoic acid, 18·85 per cent.; and aconine,
77·52 per cent.
Pure aconitine has a tube melting-point of 188·6°. The behaviour of a
sample of Merck’s aconitine in the subliming cell, which had a
melting-point of 184°, was as described at page 259.
Aconitine dissolves in water at 22° in the proportion of 1 in 4431
(_Dunstan_); it is soluble in 37 of absolute alcohol, 64 of anhydrous
ether, 5·5 parts of chloroform and benzene (_A. Jurgens_); it has basic
properties, and a cold watery solution has an alkaline reaction to
cochineal, but not to litmus nor to phenol-phthalein. Aconitine is not
precipitated by mercuric potassium iodide, but gives a voluminous
precipitate with an aqueous solution of iodine in potassium iodide.
It gives a crystalline yellow gold compound with gold chloride, which
has a melting-point of 135·5°, and according to its composition,
C₃₃H₄₅NO₁₂HAuCl₄, should give 19·9 per cent. of gold.
Aconitine is best extracted from the plant, or from organic matters
generally, by a 1 per cent. sulphuric acid; this strength is stated not
to hydrolyse aconitine if acting in the cold; after purifying the acid
liquid by shaking it with amyl alcohol, and then with chloroform,
_always operating in the cold_, the liquid is precipitated by ammonia in
very slight excess, and the liquid shaken with ether; the ether is
removed, dehydrated by standing over calcium chloride, and then
evaporated spontaneously; should the aconitine be mixed with the other
alkaloids, advantage can be taken of the method of separating
aconitine by converting it into hydrobromide, as described under
“Benzoyl-aconine.”
§ 425. =Tests for Aconitine.=--The most satisfactory and the most
delicate is the physiological test; the minutest trace of an
aconite-holding liquid, applied to the tongue or lips, causes a peculiar
numbing, tingling sensation which, once felt, can readily be remembered.
An alkaloidal substance which, heated in a tube, melts approximately
near the melting-point of aconitine, and gives off an acid vapour, would
render one suspicious of aconitine, for most alkaloids give off alkaline
vapours. Aconitine also may, by heating with dilute acids, be made to
readily yield benzoic acid, an acid easy of identification. Aconitine
dissolved in nitric acid, evaporated to dryness, and then treated with
alcoholic potash, gives off an unmistakable odour of benzoic ester.
Should there be sufficient aconitine recovered to convert it into the
gold salt, the properties of the gold salt (that is, its melting-point,
and the percentage of gold left after burning) assist materially in the
identification.
A minute quantity of aconitine dissolved in water, acidified with
acetic acid, and a particle of KI added and the solution allowed to
evaporate, gives crystals of aconitine hydriodide, from which water will
dissolve out the KI. Iodine water gives a precipitate of a reddish-brown
colour in a solution of 1 : 2000.[468]
[468] A. Jurgens, _Arch. Pharm._ (3), xxiv. 127, 128.
The chemical tests are supplementary to the physiological; if the
alkaloidal extract does not give the tingling, numbing sensation,
aconitine cannot be present.
§ 426. =Benzoyl-aconine (“isaconitine”)=, C₃₁H₄₃NO₁₁, is obtained from
aconitine by heating an aqueous solution of the sulphate or
hydrochloride in a closed tube at 120°-130° for two or three hours, a
molecule of acetic acid (9·27 per cent.) being split off, and
benzoyl-aconine left.
It may be separated from the mixed alkaloids of the _Aconitum napellus_
by dissolving in a 5 per cent. solution of hydrobromic acid (excess of
acid being avoided), precipitating with a slight excess of ammonia, and
shaking out with ether. The residue left after the ether is evaporated
chiefly consists of aconitine; it is dissolved in just sufficient
hydrobromic acid and the exactly neutral hydrobromate solution allowed
to evaporate spontaneously in a desiccator; crystals of aconitine
hydrobromide separate out, the mother liquor containing some
benzoyl-aconine and “homonapelline.” The aqueous solution which has been
exhausted with ether is now shaken out with chloroform. This chloroform
solution contains most of the benzoyl-aconine, and on separation the
residue is dissolved in just sufficient hydrochloric acid to form a
neutral solution; this solution is concentrated on the water-bath with
constant stirring, crystals of the hydrochloride form, and are filtered
off from time to time and washed with a little cold water, the washings
being added to the original liquid; the different fractions are mixed
together, and the process repeated until they have a melting-point of
268°. Benzoyl-aconine is obtained from the hydrochloride by
precipitating the aqueous solution by the addition of dilute ammonia,
and extracting the solution with ether; the solution in ether is washed
with water, dried by means of calcium chloride, and then distilled off.
Benzoyl-aconine is left as a transparent colourless non-crystalline
varnish of a melting-point near 125°.
The solution in water is alkaline to litmus. The base is readily soluble
in alcohol, in chloroform, and in ether. The alcoholic solution is
dextrorotatory. The solutions are bitter, but do not give the tingling
sensation characteristic of aconitine. The hydrochloride, the
hydrobromide, the hydriodide, and the nitrate have been obtained in a
crystalline state. The most characteristic salt is, however, the
aurochlor derivative. When aqueous solutions of benzoyl-aconine chloride
and auric chloride are mixed, a yellow precipitate is thrown down,
which (dissolved in alcohol, after being dried over calcium chloride,
and slowly evaporated in a desiccator) deposits colourless crystals
entirely different from the yellow crystals of aconitine gold chloride.
These crystals have the composition C₃₁H₄₂(AuCl₂)NO₁₁, and therefore, by
theory, should yield 22·6 per cent. of gold, and 8·2 per cent. of
chlorine.
By hydrolysis benzoyl-aconine yields benzoic acid, which can be shaken
out of an acid solution by ether and identified; one molecule of benzoic
acid is formed from one molecule of benzoyl-aconine. Twenty per cent. of
benzoic acid should, according to the formula, be obtained; Professor
Dunstan found only 18·85 per cent.[469]
[469] Professor Dunstan found, as a means of two determinations, 21·6
per cent. of gold, and 7·8 per cent. of chlorine, which comes nearer his
old formula of C₃₃H₄₄(AuCl₂)NO₁₂.--_Journ. Chem. Soc._, April 1893.
Benzoic acid in the subliming cell begins to give a cloud at about
77°-80°, and at or near 100° sublimes most rapidly.
Benzoic acid, recovered from an acid solution by shaking out with ether,
may be recognised as follows:--To the film left on evaporating off the
ether add a drop of H₂SO₄, and a few crystals of sodic nitrate, and heat
gently for a short time; pour the clear liquid into ammonia water, and
add a drop of ammonium sulphide. A red-brown colour indicates benzoic
acid. The _rationale_ of the test is as follows:--Dinitro-benzoic acid
is first formed, and next, by the action of ammonium sulphide, this is
converted into the red-brown ammonium diamidobenzoate.--E. Mohler,
_Bull. Soc. Chem._ (3), iii. 414-416.
§ 427. =Pyraconitine=, C₃₁H₄₁NO₁₀, is anhydro-benzoyl-aconine; it
differs from benzoyl-aconine by a molecule of water; picraconitine is
obtained by keeping aconitine at its melting-point (188°-190°) for some
time, when acetic acid distils over and pyraconitine is left.
Pyraconitine is an amorphous varnish, sparingly soluble in water, but
readily dissolving in alcohol, chloroform, and ether; it gives a pale
yellow precipitate with gold chloride, and forms crystalline salts with
hydriodic, hydrobromic, and hydrochloric acids. Pyraconitine readily
undergoes hydrolysis by the action of dilute acids, or by potash or
soda, or with water in a closed tube; the products are benzoic acid and
an alkaloid, to which the name of pyraconine has been given.
§ 428. =Pyraconine=, C₂₄H₃₇NO₉.--This base is anhydro-aconine, the
formula differing from aconine by one atom of water. It is amorphous,
closely resembling aconine; it is soluble in water and ether; the
aqueous solution has a somewhat sweet taste, and is lævorotatory; it
combines with acids to form crystalline salts, which are very soluble in
water.
§ 429. =Aconine=, C₂₄H₃₉NO₁₀, m.p. 132°.--Aconine does not crystallise.
Its aqueous solution is decidedly alkaline, and, like aconitine, it is
lævorotatory, although to a less degree. Its taste is bitter, but causes
no tingling sensation. Aconine is very soluble in water or alcohol, and
slightly in chloroform, but insoluble in ether or in petroleum ether. It
does, however, dissolve, in the presence of aconitine, slightly in
ether. The aqueous solutions reduce the salts of gold and silver, and
also Fehling’s solution. A solution of aconine gives precipitates with
the general alkaloidal reagents; with mercuric chloride it gives a
copious yellow precipitate, which darkens on standing.
Aconine hydrochloride, the hydriodide, the hydrobromide, and the
sulphate, have all been crystallised; solutions of these salts are
lævorotatory.
§ 430. =Commercial Aconitine and the Lethal Dose of
Aconitine.=--Commercial aconitine has in the past varied in appearance
from that of a gummy amorphous mass up to a purer kind in white
crystals.
Professor Dunstan[470] has recently examined fourteen samples, some of
them of considerable age, and only found two samples (one of English,
another of German make) which approached in melting-point and
crystalline appearance pure aconitine; the one, the English, melted at
186°-187°, and contained about 3 per cent. of benzoyl-aconine; the
other, a German specimen, was almost pure; the melting-point was 187·5°.
At the present time it is, however, not difficult to obtain fairly pure
crystalline aconitine, and to assay it accurately by determining the
proportion of acetic and benzoic acids. The physiological action of
commercial aconitine is, however, in all cases the same, the difference
being in quantitative not qualitative action; in the small doses usually
administered, the physiological action depends wholly upon the true
aconitine present, the other bases being practically without toxic
action. Professor Plugge[471] has made some researches on the fatal dose
(for the lower animals) of Petit’s, Merck’s, and Friedländer’s aconitine
nitrate, which in 1882 were the purest in commerce. He administered the
following doses to the animals mentioned:--
[470] _Journ. Chem. Soc. Trans._, 1893, 491.
[471] _Archiv de Pharm._, Jan. 7, 1882.
TABLE SHOWING FATAL DOSES (FOR ANIMALS) OF ACONITINE.
PETIT’S CRYSTALLINE ACONITINE NITRATE.
+--------------+------------+-----------+----------------------+
| Animals | Dose | Dose | |
|Experimented | Given. | per | Result. |
| upon. | | Kilogrm. | |
+--------------+------------+-----------+----------------------+
| A Frog, | ·4 mgrm. | 16·0 | Death in 60 Minutes. |
| A Rabbit, | ·8 „ | ·5-·6 | „ 30 „ |
| A Dog, | 1·6 „ | ·21 | „ 20 „ |
| „ | ·45 „ | ·10 | „ 140 „ |
| „ | ·50 „ | ·054 | Recovered. |
| „ | ·60 „ | ·075 | Recovered. |
| A Pigeon, | ·07 „ | ·22 | Death in 21 Minutes. |
+--------------+------------+-----------+----------------------+
MERCK’S ACONITINE NITRATE.
+--------------+------------+-----------+----------------------+
| Animals | Dose | Dose | |
|Experimented | Given. | per | Result. |
| upon. | | Kilogrm. | |
+--------------+------------+-----------+----------------------+
| A Frog, | ·4 mgrm. | 16 | Recovered. |
| „ | 1·0 „ | 40 | Died in 110-360 Min. |
| „ | 2·0 „ | 80 | „ 75-130 „ |
| „ | 4·0 „ | 160 | „ 50 „ |
| A Rabbit, | 3·5 „ | 2 | „ 75 „ |
| „ | 10 „ | 6·50 | „ 15 „ |
| A Dog, | 10 „ | 1·65 | „ 15 „ |
| A Pigeon, | ... | 1·65 | Recovered. |
+--------------+------------+-----------+----------------------+
FRIEDLÄNDER’S ACONITINE NITRATE.
+--------------+------------+-----------+----------------------+
| Animals | Dose | Dose | |
|Experimented | Given. | per | Result. |
| upon. | | Kilogrm. | |
+--------------+------------+-----------+----------------------+
| A Frog, | 4 mgrms. | 160 | Recovered. |
| | | | |
| „ | 10 „ | 400 } | Death in |
| „ | 20 „ | 800 } | more than |
| „ | 40 „ | 1600 } | 60 minutes. |
| | | | |
| A Rabbit, | 6 „ | 4·11 | Recovered. |
| „ | 24 „ | 18·00 | „ |
| „ | 50 „ | 85·50 | „ |
| A Dog, | 28 „ | 6·00 | „ |
| A Pigeon, | 10 „ | 33·4 | „ |
+--------------+------------+-----------+----------------------+
The conclusions Plugge draws from his researches are that Petit’s
aconitine was at least eight times stronger than that of Merck, and
seventy times more toxic than that of Friedländer, while Merck’s
“aconitine again was twenty to thirty times stronger than
Friedländer’s.” He was inclined to put seven commercial samples which he
has examined in the following diminishing order of toxicity:--(1)
Petit’s crystalline aconitine nitrate; (2) Morson’s aconitine nitrate;
(3) Hottot’s aconitine nitrate; (4) Hopkins & Williams’ pseudaconitine;
(5) Merck’s aconitine nitrate; (6) Schuchart’s aconitine sulphate; and
(7) Friedländer’s aconitine nitrate.
From a study of Dr. Harley’s experiments,[472] however, made a few years
ago, there would appear to have been but little difference between the
activity of Petit’s and Morson’s aconitine. Dr. Harley experimented on a
young cat, 3 lbs. in weight, and nearly killed it with a 1/1000 of a
grain of Morson’s aconitine; two other cats, also weighing 3 lbs. each,
died in seven and a half hours and three-quarters of an hour
respectively, killed from a subcutaneous dose of of a grain. Reducing
these values to the ordinary equivalents, the dose, after which the cat
recovered with difficulty, is equal to about ·048 mgrm. per kilo.,
while a certainly fatal dose is ·092 mgrm. per kilo.; therefore, it
seems likely that the least fatal dose for Morson’s, as for Petit’s, is
some number between ·075 and ·09 mgrm. per kilo.
[472] “On the Action and Use of Aconitine,” _St. Thos. Hosp. Report_,
1874.
Man is evidently more sensitive to aconitine than any of the dogs or
cats experimented upon, since, in the German cases to be recorded, 1·6
mgrm. of Petit’s aconitine nitrate, taken by the mouth, gave rise to
symptoms so violent that it was evidently a dangerous dose, while 4
mgrms. were rapidly fatal; but if man took the same amount per kilo. as
dogs or cats, he would require a little over 6 mgrms. to be certainly
fatal. It seems, then, from the evidence obtainable, that ·03 grain (2
mgrms.) is about the least fatal dose for an adult man of standard
weight. This dose is equal to ·028 mgrm. per kilo., and, of course,
refers either to Morson’s aconitine or French aconitine, the alkaloid
being taken by the mouth. If given by subcutaneous injection, probably
1·5 mgrm. would kill, for the whole of the poison is then thrown on the
circulation at one time, and there is no chance of its elimination by
vomiting.
The lethal dose of the pure alkaloid being even approximately settled,
it is possible to get a more exact idea as to the suitable medicinal
dose of the tincture and extract, and also to study more profitably the
“quantitative toxicity.” The English officinal tincture, although
variable in strength, may for our purposes be regarded as averaging 1
per cent. of alkaloid--that is, in every 100 parts by volume there will
be 1 part of the alkaloid by weight, and Fleming’s tincture may be
considered as one-third stronger, containing in every 100 parts 1·3 part
of alkaloid. The medicinal dose of the P.B. tincture is laid down as
from 5 to 15 min.--equal to from ·005 to ·015 grain of aconitine. The
German pharmacopœia gives the maximum single dose as 1 c.c. (say 15
mins.), and the maximum quantity to be taken in the twenty-four hours as
four times that quantity. As before stated, 2 mgrms. (·030 grain) of
aconitine being considered a fatal dose, this is equivalent to about 2
c.c. (30 mins.) of the P.B. tincture, or to 1·2 c.c. (20 mins.) of
Fleming’s tincture in a single dose; and on these theoretical grounds I
should consider this dose dangerous, and in the absence of prompt
treatment likely to be fatal to an adult man. The usual least fatal dose
laid down in medical toxicological works, however, is greater than
this--viz., 3·75 c.c. (a drachm).
In 1863 a woman took 70 minims of Fleming’s tincture, and a grain of
acetate of morphine, and died in about four hours; but as this was a
complex case of poisoning, it is not of much value. Fifteen minims of
the tincture caused very serious symptoms in the case of a woman under
the care of Dr. Topham,[473] the effects lasting many hours. Probably
the smallest quantity of the tincture recorded as having destroyed life
is in the case of Dr. Male, of Birmingham.[474] He died from the
effects of 80 drops taken in ten doses, extending over a period of four
days--the largest dose at any one time being 10 drops, the total
quantity would perhaps equal ·08 grain of aconitine.
[473] _Lancet_, July 19, 1851, p. 56.
[474] _Med. Gaz._, vol. xxxvi. p. 861, quoted by Taylor, _Prin. of Med.
Juris._, vol. i. p. 426.
The P.B. extract is not a very satisfactory preparation, varying much in
strength. It may be taken to average about ·6 per cent., and if so,
applying the same reasoning as before, from ·26 to ·32 grm. (4 to 5
grains) would be a fatal dose.[475] On the other hand, there is an
alcoholic extract which is very powerful, and averages 5 per cent. of
aconitine: 40 mgrms. (·6 grain) of this extract would be likely to be
fatal. With regard to the root itself, 3·8 grms. (60 grains) have been
known to produce death, and from the average alkaloidal contents it is
probable that ·648 grm. (10 grains) would be a highly dangerous dose.
Dunstan’s researches will now alter probably the whole of the pharmacy
of aconite, and the tendency will be to make the preparations of greater
activity, and, consequently, to make the dangerous doses smaller than
formerly.
[475] But there is a case reported by Dr. Vachell, of Cardiff, in which
2 grains of extract of aconite taken in pills proved fatal. Now 2 grains
is the medicinal dose, laid down as a maximum in the pharmacopœia; a
complete revolution is, therefore, necessary in the use of these active
remedies. No extract or tincture should be used until its approximate
strength in active principles is determined.
§ 431. =Effects of Aconitine on Animal Life.=--There are few substances
which have been experimented upon in such a variety of ways and upon so
many classes of animals as aconitine in different forms; but there does
not seem to be any essential difference in the symptoms produced in
different animals save that which is explained by the organisation of
the life-form under experiment.
=Insects.=--The author has made experiments with the active principles
of aconite upon blow-flies. An extract was made by allowing the ordinary
tincture to evaporate spontaneously at the temperature of the
atmosphere. If a minute dot of this is placed upon the head of a
blow-fly, absorption of the active principle takes place in from fifteen
to thirty minutes, and marked symptoms result. The symptoms consist
essentially of muscular weakness, inability to fly, and to walk up
perpendicular surfaces; there is also, in all cases, a curious
entanglement of the legs, and very often extrusion of the proboscis;
trembling of the legs and muscular twitchings are frequent. A
progressive paralysis terminates in from four to five hours in death;
the death is generally so gradual that it is difficult to know when the
event occurs, but in one case there were violent movements of the body,
and sudden death.[476]
[476] It may be well to quote in full a typical experiment. Six P.M., a
little extract smeared on the head of a blow-fly. Forty-five minutes
after--makes no attempt to fly, great muscular weakness, no trembling or
convulsive movements. Fifty minutes after--partial paralysis of right
half of body, so that the fly, on moving, goes in a circular direction,
the second pair of legs are curiously bent forward and useless; the
wings seem fairly strong. Seventy-five minutes--fly very dull, always in
one spot, without movement; when placed on a horizontal glass surface,
and the glass then very slowly inclined, until it is at last quite
perpendicular, the fly falls. There is now a strange entanglement of the
legs. 125 minutes--perfectly paralysed; 145 minutes--dead.
=Fish.=--The action on fish has been studied by Schulz and Praag. There
is rapid loss of power and diminished breathing; the respiration seems
difficult, and the fish rapidly die.
=Reptiles--Frogs.=--The most recent experiments on frogs are those of
Plugge, and although his interpretation of the phenomena in some points
is different from that of previous observers, the symptoms themselves
are, as might have been expected, not different from those described by
Achscharumow, L. v. Praag, and others. Plugge found no qualitative
difference in the action of any of the commercial samples of aconitine.
This fact gives the necessary value to all the old experiments, for we
now know that, although they were performed with impure or weak
preparations, yet there is no reason to believe that the symptoms
described were due to any other but the alkaloid aconitine in varying
degrees of purity or dilution. Frogs show very quickly signs of weakness
in the muscular power; the respiration invariably becomes laboured, and
ceases after a few minutes; the heart’s action becomes slowed,
irregular, and then stops in diastole. The poisoned heart, while still
pulsating, cannot be arrested either by electrical stimulation of the
vagus or by irritation of the sinus, nor when once arrested can any
further contraction be excited in it. Opening of the mouth and apparent
efforts to vomit, Plugge observed both with _Rana esculenta_ and _Rana
temporaria_. He considers them almost invariable signs of aconitine
poisoning. A separation of mucus from the surface of the body of the
frog is also very constantly observed. Dilatation of the pupils is
frequent, but not constant; there may be convulsions, both of a clonic
and tonic character, before death, but fibrillar twitchings are seldom.
(With regard to the dose required to affect frogs, see _ante_, pp. 355
and 356.)
=Birds.=--There is a discrepancy in the descriptions of the action of
aconitine on birds. L. v. Praag thought the respiration and circulation
but little affected at first; while Achscharumow witnessed in pigeons
dyspnœa, dilatation of the pupils, vomiting, shivering, and paresis. It
may be taken that the usual symptoms observed are some difficulty in
breathing, a diminution of temperature, a loss of muscular power
generally (but not constantly), dilatation of the pupils, and
convulsions before death.
=Mammals.=--The effects vary somewhat, according to the dose. Very large
doses kill rabbits rapidly. They fall on their sides, are violently
convulsed, and die in an asphyxiated condition; but with smaller doses
the phenomena first observed are generally to be referred to the
respiration. Thus, in an experiment on the horse, Dr. Harley found that
the subcutaneous administration of ·6 mgrm. (·01 grain) caused in a
weakly colt some acceleration of the pulse and a partial paralysis of
the dilator narium. Double the quantity given to the same animal some
time after, caused, in six hours and a half, some muscular weakness, and
an evident respiratory trouble. The horse recovered in eighteen hours.
2·7 mgrms. (1/24 grain) given in the same way, after a long interval of
time, caused, at the end of an hour, more pronounced symptoms; the
pulse, at the commencement 50, rose in an hour and a half to 68, then
the respiration became audible and difficult. In an hour and
three-quarters there were great restlessness and diminution of muscular
power. Two hours after the injection the muscular weakness increased so
much that the horse fell down; he was also convulsed. After eight hours
he began to improve. In another experiment, 32·4 mgrms. (½ grain) killed
a sturdy entire horse in two hours and twenty minutes, the symptoms
commencing within the hour, and consisting of difficulty of breathing,
irregularity of the heart’s action, and convulsions.
The general picture of the effects of fatal, but not excessive, doses
given to dogs, cats, rabbits, &c., resembles closely that already
described. The heart’s action is at first slowed, then becomes quick and
irregular, there is dyspnœa, progressive paralysis of the muscular
power, convulsions, and death in asphyxia. Vomiting is frequently
observed, sometimes salivation, and very often dilatation of the pupil.
Sometimes the latter is abnormally active, dilating and contracting
alternately. Diarrhœa also occurs in a few cases. Vomiting is more
frequent when the poison is taken by the mouth than when administered
subcutaneously.[477]
[477] The more important physiological researches on the action of
aconite are contained in the following works and papers:--
FLEMING, A.--_An Inquiry into the Physiological and Medicinal
Properties of the Aconitum napellus_, to which are added
observations on several other species of aconite, 8vo, Lond., 1845.
SCHULZ, F. W.--_De Aconitini Effectu in Organismum Animalium._
V. PRAAG.--_Arch. f. Path. Anat._, vii. p. 438, 1854.
HOTTOT, E.--_De l’Aconitine et de ses Effets Physiologiques_, 4to,
Paris, 1863.
ACHSCHARUMOW.--_Arch. f. Anatom. u. Physiol._, 1866.
BÖHN.--_Herzgifte_, 1871.
EWERS, C.--_Ueber die physiologischen Wirkungen des aus Aconitum
ferox dargestellten Aconitins_ (_Pseudoaconitin, Aconitinum
anglicum, Nepalin_), 8vo, Dorpat, 1873.
GUILAUD.--_De l’Aconite et de l’Aconitine_, 4to, Montpellier, 1874.
FRANCHESCHINI, M. A.--_Contribution a l’Étude de l’Action
Physiologique et Thérapeutique de l’Aconitine_, 4to, Paris, 1875.
LEWIN.--_Exp. Untersuch. über die Wirkung d. Aconitins auf’s Herz.
Diss._, Berlin, 1875.
GIULINI, P.--_Experimentelle Untersuchungen ueber die Wirkung des
Aconitins auf das Nervensystem, das Herz, u. die Athmung_, 8vo,
Erlangen, 1876.
HARLEY, DR. JOHN.--“On the Action and Uses of Aconitia,” _St. Thos.
Hosp. Reports_, 1874.
V. SCHROFF, C. Jr.--_Beitrag zur Kenntniss des Aconit._, 8vo, Wien,
1876.
PLUGGE, P. C.--“Untersuchungen ueber die physiologische Wirkung
verschiedener Handelssorten von Aconitin, u. Pseudoaconitin auf
Muskeln u. Nerven,” _Virch. Archiv_, Bd. 87, 1882, S. 410.
§ 432. =Statistics.=--During the ten years, 1883-92, there were recorded
in England and Wales, 40 accidental deaths from the various forms of
aconite (19 males, 21 females); and 19 suicidal deaths (9 males, 10
females) from the same cause, which makes a total of 59.
§ 433. =Effects on Man.=--I have collected from European medical
literature, 87 cases of poisoning by aconite in some form or other.
These comprise only 2 cases of murder, 7 of suicide, and 77 which were
more or less accidental. Six of the cases were from the use of the
alkaloid itself; 10 were from the root; in two cases children eat the
flowers; in 1, the leaves of the plant were cooked and eaten by mistake;
in 7, the tincture was mistaken for brandy, sherry, or liqueur; the
remainder were caused by the tincture, the liniment, or the extract.
§ 434. =Poisoning by the Root.=--A case of murder which occurred some
years ago in America, and also the Irish case which took place in 1841
(_Reg._ v. _M’Conkey_), were, until the recent trial of Lamson, the only
instances among English-speaking people of the use of aconite for
criminal purposes; but if we turn to the Indian records, we find that it
has been largely used from the earliest times as a destroyer of human
life. In 1842 a tank of water destined for the use of the British army
in pursuit of the retreating Burmese, was poisoned by intentional
contamination with the bruised root of _Aconitum ferox_; it was
fortunately discovered before any harm resulted. A preparation of the
root is used in all the hill districts of India to poison arrows for the
destruction of wild beasts. A Lepcha described the root to a British
officer as being “useful to sportsmen for destroying elephants and
tigers, useful to the rich for putting troublesome relations out of the
way, and useful to jealous husbands for the purpose of destroying
faithless wives.” From the recorded cases, the powdered root, mixed with
food, or the same substance steeped in spirituous liquor, is usually the
part chosen for administration. In M’Conkey’s case, the man’s wife
purchased powdered aconite root, mixed it with pepper, and strewed it
over some greens, which she cooked and gave to him. The man complained
of the sharp taste of the greens, and soon after the meal vomited, and
suffered from purging, became delirious with lock-jaw, and clenching of
the hands; he died in about three hours. The chief noticeable
_post-mortem_ appearance was a bright red colour of the mucous membrane
of the stomach.
The symptoms in this case were, in some respects, different from those
met with in other cases of poisoning by the root. A typical case is
given by Dr. Chevers (_op. cit._), in which a man had taken by mistake a
small portion of aconite root. Immediately after chewing it he felt a
sweetish taste, followed immediately by tingling of the lips and tongue,
numbness of the face, and severe vomiting. On admission to hospital he
was extremely restless, tossing his limbs about in all directions and
constantly changing his position. He complained of a burning sensation
in the stomach, and a tingling and numbness in every part of the body,
excepting his legs. The tingling was specially marked in the face and
tongue--so much so that he was constantly moving the latter to and fro
in order to scratch it against the teeth. Retching and vomiting occurred
almost incessantly, and he constantly placed his hand over the cardiac
region. His face was anxious, the eyes suffused, the lips pale and
exsanguine, the eyelids swollen, moderately dilated, and insensible to
the stimulus of light; the respiration was laboured, 64 in a minute; the
pulse 66, small and feeble. There was inability to walk from loss of
muscular power, but the man was perfectly conscious. The stomach-pump
was used, and albumen and milk administered. Three and three-quarter
hours after taking the root the symptoms were increased in severity. The
tongue was red and swollen, the pulse intermittent, feeble, and slower.
The tingling and numbness had extended to the legs. On examining the
condition of the external sensibility with a pair of scissors, it was
found that, on fully separating the blades and bringing the points in
contact with the skin over the arms and forearms, he felt them as one,
although they were 4 inches apart. But the sensibility of the thighs and
legs was less obtuse, for he could feel the two points distinctly when
they were 4 inches apart, and continued to do so until the distance
between the points fell short of 2¾ inches. He began to improve about
the ninth hour, and gradually recovered, although he suffered for one or
two days from a slight diarrhœa. As in the case detailed (p. 363), no
water was passed for a long time, as if the bladder early lost its
power.
§ 435. =Poisoning by the Alkaloid Aconitine.=--Probably the earliest
instance on record is the case related by Dr. Golding Bird in 1848.[478]
What kind of aconitine was then in commerce I know not, and since
apparently a person of considerable social rank was the subject of the
poisoning, the case has been imperfectly reported. It seems, however,
that, whether for purposes of suicide, or experiment, or as a medicine,
two grains and a half of aconitine were swallowed. The symptoms were
very violent, consisting of vomiting, collapse, and attacks of muscular
spasm; the narrator describes the vomiting as peculiar. “It, perhaps,
hardly deserved that title; the patient was seized with a kind of
general spasm, during which he convulsively turned upon his abdomen,
and with an intense contraction of the abdominal muscles, he jerked out,
as it were, with a loud shout the contents of his stomach, dependent
apparently on the sudden contraction of the diaphragm.” On attempting to
make him swallow any fluid, a fearful spasm of the throat was produced;
it reminded his medical attendants of hydrophobia. The patient recovered
completely within twenty-four hours.
[478] _Lancet_, vol. i. p. 14.
One of three cases reported by Dr. Albert Busscher,[479] of poisoning by
aconitine nitrate, possesses all the exact details of an intentional
experiment, and is of permanent value to toxicological literature.
[479] _Intoxicationsfälle durch Aconitin Nitricum Gallicum, nebst
Sections Bericht_, von Dr. Albert Busscher; _Berl. klinische
Wochenschrift_, 1880, No. 24, pp. 338, 356.
A labourer of Beerta, sixty-one years of age, thin, and of somewhat weak
constitution, suffered from neuralgia and a slight intermittent fever;
Dr. Carl Meyer prescribed for his ailment:--
℞. Aconiti Nitrici, 2 grm.
Tr. Chenopodii Ambrosioid., 100 grms. M.D.S.
Twenty drops to be taken four times daily. The patient was instructed
verbally by Dr. Meyer to increase the dose until he attained a maximum
of sixty drops per day.
The doses which the man actually took, and the time of taking them, are
conveniently thrown into a tabular form as follows:--
No. 1. March 14, 7 P.M., 5 drops equal to aconitine nitrate, ·4 mgrm.
„ 2. „ 9 P.M., 20 „ „ „ 1·6 „
„ 3. March 15, 8 A.M., 20 „ „ „ 1·6 „
„ 4. „ 11 A.M., 20 „ „ „ 1·6 „
„ 5. „ 4 P.M., 20 „ „ „ 1·6 „
„ 6. „ 9 P.M., 20 „ „ „ 1·6 „
„ 7. March 16, 10 P.M., 10 „ „ „ ·8 „
In the whole seven doses, which were distributed over forty-eight hours,
he took 9·2 mgrms. (·14 grain) of aconitine nitrate.
On taking dose No. 1, he experienced a feeling of constriction
(_Zusammenziehung_), and burning spreading from the mouth to the
stomach, but this after a little while subsided. Two hours afterwards he
took No. 2, four times the quantity of No. 1. This produced the same
immediate symptoms, but soon he became cold, and felt very ill. He had
an anxious oppressive feeling about the chest, with a burning feeling
about the throat; the whole body was covered with a cold sweat, his
sight failed, he became giddy, there was excessive muscular weakness, he
felt as if he had lost power over his limbs, he had great difficulty in
breathing. During the night he passed no water, nor felt a desire to do
so. About half an hour after he had taken the medicine, he began to
vomit violently, which relieved him much; he then fell asleep.
Dose No. 3, equal as before to 1·6 mgrm., he took in the morning. He
experienced almost exactly the same symptoms as before, but convulsions
were added, especially of the face; the eyes were also prominent; twenty
minutes after he had taken the dose, vomiting came on, after which he
again felt better.
He took dose No. 4, and had the same repetition of symptoms, but in the
interval between the doses he felt weaker and weaker; he had no energy,
and felt as if paralysed. No. 5 was taken, and produced, like the
others, vomiting, after which he felt relieved. Neither he nor his wife
seemed all this time to have had any suspicion that the medicine was
really doing harm, but thought that the effects were due to its constant
rejection by vomiting, so, in order to prevent vomiting with No. 6, he
drank much cold water. After thus taking the medicine, the patient
seemed to fall into a kind of slumber, with great restlessness; about an
hour and a half afterwards he cried, “I am chilled; my heart, my heart
is terribly cold. I am dying; I am poisoned.” His whole body was covered
with perspiration; he was now convulsed, and lost sight and hearing; his
eyes were shut, his lips cracked and dry, he could scarcely open his
mouth, and he was extremely cold, and thought he was dying. The
breathing was difficult and rattling; from time to time the muscular
spasms came on. His wife now made a large quantity of hot strong black
tea, which she got him to drink with great difficulty; although it was
hot, he did not know whether it was hot or cold. About five minutes
afterwards he vomited, and did so several times; this apparently
relieved him, and he sank into a quiet sleep; during the night he did
not urinate. In the morning the wife went to Dr. Carl Meyer, described
the symptoms, and accused the medicine. So convinced was Dr. Meyer that
the medicine did not cause the symptoms, that he poured out a quantity
of the same, equal to 4 mgrms. of aconitine nitrate, and took it himself
in some wine, to show that it was harmless, and ordered them to go on
with it. The unhappy physician died of aconitine poisoning five hours
after taking the medicine.[480] In the meantime, the woman went home,
and her husband actually took a seventh, but smaller dose, which
produced similar symptoms to the former, but of little severity; no more
was taken.
[480] The symptoms suffered by Dr. Meyer are to be found in _Neder.
Tijdschrift van Geneeskunde_, 1880, No. 16.
The absence of diarrhœa, and of the pricking sensations so often
described, is in this case noteworthy. Both diarrhœa and formication
were also absent in a third case reported by Dr. Busscher in the same
paper.
§ 436. The most important criminal case is undoubtedly that of
Lamson:--At the Central Criminal Court, in March, 1882, George Henry
Lamson, surgeon, was convicted of the murder of his brother-in-law,
Percy Malcolm John. The victim was a weakly youth of eighteen years of
age, paralysed in his lower limbs from old standing spinal disease. The
motive for perpetrating the crime was that Lamson, through his wife
(Malcolm John’s sister), would receive, on the death of his
brother-in-law, a sum of £1500, and, according to the evidence, it is
probable that there had been one or more previous attempts by Lamson on
the life of the youth with aconitine given in pills and in powders.
However this may be, on November 24, 1880, Lamson purchased 2 grains of
aconitine, came down on Dec. 3 to the school where the lad was placed,
had an interview with his brother-in-law, and, in the presence of the
head-master, gave Malcolm John a capsule, which he filled then and there
with some white powder, presumed at the time to be sugar. Lamson only
stayed altogether twenty minutes in the house, and directly after he saw
his brother-in-law swallow the capsule, he left. Within fifteen minutes
Malcolm John became unwell, saying that he felt as if he had an attack
of heart-burn, and then that he felt the same as when his brother-in-law
had on a former occasion given him a quinine pill. Violent vomiting soon
set in, and he complained of pains in his stomach, a sense of
constriction in his throat, and of being unable to swallow. He was very
restless--so much so that he had to be restrained by force from injuring
himself. There was delirium a few minutes before death, which took place
about three hours and three-quarters after swallowing the fatal dose.
The _post-mortem_ appearances essentially consisted of redness of the
greater curvature of the stomach, and the posterior portion of the same
organ. In one part there was a little pit, as if a blister had broken;
the rest of the viscera were congested, and the brain also slightly
congested.[481]
[481] To these cases of poisoning by the alkaloid aconitine may be added
one recorded in Bouchardat’s _Annuaire de Thérapeutie_, 1881, p. 276.
The case in itself is of but little importance, save to illustrate the
great danger in permitting the dispensing of such active remedies of
varying strength. A gentleman suffering from “angina pectoris” was
prescribed “Hottot’s aconitine” in granules, and directed carefully to
increase the dose up to four granules, according to the effect produced.
The prescription was taken to a pharmacist, who, instead of supplying
Hottot’s aconitine, supplied some other of unknown origin. The medicine
was taken daily, and the dose raised to four granules, which were taken
with benefit until the whole was exhausted. He then went to Hottot’s
establishment, and had a fresh supply, presumably of the same substance,
but a very little time after he had taken his usual dose of four
granules, he suffered from symptoms of aconitine poisoning, headache,
vertigo, feebleness of the voice, and muscular weakness, and was
alarmingly ill. He recovered after some hours of medical treatment.
§ 437. The symptoms of poisoning by the tincture, extract, or other
preparation, do not differ from those detailed. As unusual effects,
occasionally seen, may be noted profound unconsciousness lasting for
two hours (Topham’s case), violent twitching of the muscles of the
face, opisthotonos, and violent convulsions. It is important to
distinguish the symptoms which are not constant from those which are
constant, or nearly so. The tingling and creeping sensations about the
tongue, throat, lips, &c., are not constant; they certainly were not
present in the remarkable German case cited at p. 363. Speaking
generally, they seem more likely to occur after taking the root or the
ordinary medicinal preparations. A dilated state of the pupil is by no
means constant, and not to be relied upon. Diarrhœa is seen after taking
the root or tincture by the stomach, but is often absent. In short, the
only constant symptoms are difficulty of breathing, progressive muscular
weakness, generally vomiting, and a weak intermittent pulse.
§ 438. =Physiological Action.=--Aconitine, according to Dr. S. Ringer,
is a protoplasmic poison, destroying the functions of all nitrogenous
tissue--first of the central nervous system, next of the nerves, and
last of the muscles. Aconitine without doubt acts powerfully on the
heart, ultimately paralysing it; there is first a slowing of the pulse,
ascribed to a central excitation of the vagus; then a quickening, due to
paralysis of the peripheral termination of the vagus in the heart;
lastly, the heart’s action becomes slow, irregular, and weak, and the
blood-pressure sinks. The dyspnœa and convulsions are the usual result,
seen among all warm-blooded animals, of the heart affection. Plugge
found that the motor nerves, and more especially their intra-muscular
terminations, were always paralysed; but if the dose was small the
paralysis might be incomplete. Bœhm and Wartmann, on the other hand,
considered that the motor paralysis had a central origin, a view not
supported by recent research. The action of aconitine in this way
resembles curare. The muscles themselves preserve their irritability,
even after doses of aconitine which are five to ten times larger than
those by which the nerve terminations are paralysed.
§ 439. =Post-mortem Appearances.=--Among animals (mammals) the
appearances most constantly observed have been hyperæmia of the cerebral
membranes and brain, a fulness of the large veins, the blood generally
fluid--sometimes hyperæmia of the liver, sometimes not. When aconitine
has been administered subcutaneously, there have been no inflammatory
appearances in the stomach and bowels.
In the case of Dr. Carl Meyer, who died in five hours from swallowing 4
mgrms. of aconitine nitrate, the corpse was of a marble paleness, the
pupils moderately dilated. The colour of the large intestine was pale;
the duodenum was much congested, the congestion being most intense the
nearer to the stomach; the mucous membrane of the stomach itself was
strongly hyperæmic, being of an intense red colour; the spleen was
enlarged, filled with much dark blood. The liver and kidneys were
deeply congested, the lungs also congested; the right ventricle of the
heart was distended with blood; in the pericardium there was a quantity
of bloody serum. The brain was generally blood-red; in the cerebral
hemispheres there were several large circumscribed subarachnoid
extravasations. The substance of the brain on section showed many red
bloody points.
In a case recorded by Taylor, in which a man died in three hours from
eating a small quantity of aconitine root, the only morbid appearance
found was a slight reddish-brown patch on the cardiac end of the
stomach, of the size of half a crown; all the other organs being
healthy.
§ 440. =Separation of Aconitine from the Contents of the Stomach or the
Organs.=--It would appear certain that in all operations for the
separation of aconite alkaloids (whether from the organic matters which
make up the plant, or from those constituting animal tissues), mineral
acids and a high heat should be avoided. A 1 per cent. sulphuric acid
does not, however, hydrolyse, if acting in the cold, so that the process
already given, p. 352, may be followed.
The chemical examination in the Lamson case was entrusted to Dr.
Stevenson, assisted by Dr. Dupré, and was conducted on the principles
detailed. The contents of the stomach were treated with alcohol, and
digested at the ordinary temperature of the atmosphere; the contents
were already acid, so no acid in this first operation was added. The
mixture stood for two days and was then filtered. The insoluble portion
was now exhausted by alcohol, faintly acidulated by tartaric acid, and
warmed to 60°; cooled and filtered, the insoluble part being washed
again with alcohol. The two portions--that is, the spirituous extract
acid from acids pre-existing in the contents of the stomach, and the
alcohol acidified by tartaric acid--were evaporated down separately,
exhausted by absolute alcohol, the solutions filtered, evaporated, and
the residue dissolved in water. The two aqueous solutions were now
mixed, and shaken up with ether, which, as the solution was acid, would
not remove any alkaloid, but might remove various impurities; the
residue, after being thus partially purified by ether, was alkalised by
sodic carbonate, and the alkaloid extracted by a mixture of chloroform
and ether. On evaporation of the chloroform and ether, the resulting
extract was tested physiologically by tasting, and also by injections
into mice. By means analogous to those detailed, the experts isolated
aconitine from the vomit, the stomach, liver, spleen, and urine, and
also a minute quantity of morphine, which had been administered to the
patient to subdue the pain during his fatal attack. When tasted, the
peculiar numbing, tingling sensation lasted many hours. These extracts
were relied upon as evidence, for their physiological effect was
identical with that produced by aconitine. For example, the extract
obtained from the urine caused symptoms to commence in a mouse in two
minutes, and death in thirty minutes, and the symptoms observed by
injecting a mouse with known aconitine coincided in every particular
with the symptoms produced by the extraction from the urine.
With regard to the manner of using “_life tests_,” since in most cases
extremely small quantities of the active principle will have to be
identified, the choice is limited to small animals, and it is better to
use mice or birds, rather than reptiles. In the Lamson case,
subcutaneous injections were employed, but it is a question whether
there is not less error in administering it by the mouth. If two healthy
mice are taken, and the one fed with a little meal, to which a weighed
quantity of the extract under experiment has been added, while to the
other some meal mixed with a supposed equal dose of aconitine is given,
then the symptoms may be compared; and several objections to any
operative proceeding on such small animals are obviated. It is certain
that any extract which causes distinct numbness of the lips will contain
enough of the poison to kill a small bird or a mouse, if administered in
the ordinary way.[482]
[482] Dr. A. Langaard has described a species of aconite root, named by
the Japanese _Kŭsa-ūsū_. From his experiments on frogs and rabbits, its
physiological action seems not to differ from that of aconitine
generally.--_Ueber eine Art Japanische Akonit-knollen, Kŭsa-ūsū genannt,
u. über das in denselben vorkommende Akonitin. Virchow’s Archiv_, B. 79,
1880, p. 229.
VI.--The Mydriatic Group of
Alkaloids--Atropine--Hyoscyamine--Solanine--Cytisine.
1. ATROPINE.
§ 441. =Atropine= (=Daturine=), C₁₇H₂₃NO₃.--This important alkaloid has
been found in all parts of the _Atropa belladonna_, or deadly
nightshade, and in all the species of _Datura_.
The _Atropa belladonna_ is indigenous, and may be found in some parts of
England, although it cannot be said to be very common. It belongs to the
_Solanaceæ_, and is a herbaceous plant with broadly ovate entire leaves,
and lurid-purple axillary flowers on short stalks; the berries are
violet-black, and the whole of the plant is highly poisonous. The juice
of the leaves stains paper a purple colour. The seeds are very small,
kidney-shaped, weighing about 90 to the grain; they are covered closely
with small, round projections, and are easily identified by an expert,
who may be supposed to have at hand (as is most essential) samples of
different poisonous seeds for comparison. The nightshade owes its
poisonous properties to _atropine_.
The yield of the different parts of belladonna, according to
Gunther,[483] is as follows:--
[483] _Pharm. Zeitschr. f. Russl._, Feb., 1869; Dragendorff, _Die
chemische Werthbestimmung einiger starkwirkenden Droguen_, St.
Petersburg, 1874.
TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE BELLADONNA
PLANT.
+-------------+----------------------+----------------------+
| |Quantity of Alkaloids |Quantity of Alkaloids |
| | in the Fresh | in the Dry |
| | Substance, per cent. | Substance, per cent. |
| +-----------+----------+-----------+----------+
| | (_a._) By |(_b._) By | (_a._) By |(_b._) By |
| | Weighing. |Titration.| Weighing. |Titration.|
+-------------+-----------+----------+-----------+----------+
|Leaves, | 0·2022 | 0·20072 | 0·838 | 0·828 |
|Stalk, | 0·0422 | ... | 0·146 | ... |
|Ripe fruit, | 0·2128 | 0·20258 | 0·821 | 0·805 |
|Seed, | 0·26676 | ... | 0·407 | ... |
|Unripe fruit,| 0·1870 | 0·1930 | 0·955 | 0·955 |
|Root, | 0·0792 | ... | 0·210 | ... |
+-------------+-----------+----------+-----------+----------+
Atropine appears to exist in the plant in combination with malic acid.
According to a research by Ladenburg, hyoscyamine is associated with
atropine, both in the Belladonna and Datura plants.[484]
[484] _Ber. der deutsch. Chem. Ges._, Bd. 13.
From a research by W. Schütte,[485] it appears that the younger roots of
wild belladonna contain hyoscyamine only, whilst the older roots contain
atropine as well as hyoscyamine, but only in small proportion; the same
was observed to be the case in the older cultivated roots.
[485] _Arch. Pharm._, ccxxix., 492-531; _Journ. Chem. Soc._ (abstract),
February 1892, 231.
The ripe berries of cultivated _Atropa belladonna nigra_ contain
atropine and hyoscyamine; those of the wild plant contain atropine only;
the ripe fruit of _Atropa belladonna lutea_ contains only atropine and
another base, perhaps identical with atropamine; the unripe fruit of
wild _Atropa belladonna nigra_ contains hyoscyamine, with only a small
quantity of atropine.
The leaves of the yellow and black-fruited wild _Atropa belladonna_
contain hyoscyamine and atropine, the latter being in small quantity
only.
Fresh and old seeds of _Datura Stramonium_ contain chiefly hyoscyamine;
small quantities of atropine and scopolamine are also present.
§ 442. =The Datura Stramonium or Thorn-apple= is also indigenous in the
British Islands, but, like belladonna, it cannot be considered a common
plant. Datura belongs to the Solanaceæ; it grows from 1 to 2 feet in
height, and is found in waste places. The leaves are smooth, the flowers
white; the fruit is densely spinous (hence the name thorn-apple), and is
divided into four dissepiments below, two at the top, and containing
many seeds.
The _Datura_, or the _Dhatura_-plants, of India have in that country a
great toxicological significance, the white-flowered datura, or _Datura
alba_, growing plentifully in waste places, especially about Madras. The
purple-coloured variety, or _Datura fastuosa_, is also common in certain
parts. There is a third variety, the _Datura atrox_, found about the
coast of Malabar. The seeds of the white datura have been mistaken in
India for those of capsicum. The following are some of the most marked
differences:--
SEEDS OF THE COMMON OR WHITE SEEDS OF CAPSICUM.
DATURA.
(1.) Outline angular. Outline rounded.
(2.) Attached to the placenta by a Attached to the placenta by a
large, white, fleshy mass separ- cord from a prominence on the
ating easily, leaving a deep concave border of the seed.
furrow along half the length of
the seed’s concave border.
(3.) Surface scabrous, almost re- Uniformly scabrous, the sides
ticulate, except on the two com- being equally rough with the
pressed sides, where it has borders.
become almost glaucous from
pressure of the neighbouring
seeds.
(4.) Convex border thick and Convex border thickened, but
bulged with a longitudinal depres- uniformly rounded.
sion between the bulgings, caused
by the compression of the two
sides.
(5.) A suitable section shows the The embryo, exposed by a suitable
embryo curved and twisted in the section, is seen to resemble in
fleshy albumen. outline very closely the figure
6.
(6.) The taste of the datura seeds The taste of capsicum is pungent;
is very feebly bitter. The watery a decoction irritates the eye
decoction causes dilatation of the much, but does not cause dilata-
pupil. tion of the pupil.
The identity of the active principle in both the datura and belladonna
tribes is now completely established.[486]
[486] See a research by Ernst Schmidt, “Ueber die Alkaloide der
Belladonna-Wurzel u. des Stechapfel-Samens,” _Lieb. Annl._, Bd. 208,
1881.
§ 443. =Pharmaceutical Preparations.=--(_a._) _Of the leaves. Extract
of Belladonna._--This contains, according to Squire,[487a] from 0·73 to
1·7 per cent. of total alkaloids. _Belladonna Juice_ (_succus
belladonnæ_).--Strength in alkaloid about 0·05 per cent. _Tincture of
Belladonna._--Half the strength of the juice, and therefore yielding
about 0·025 per cent. of alkaloid.
[487a] _Companion to the British Pharmacopœia_, 1894.
(_b._) _Belladonna Root.--Belladonna plaster_ contains 20 per
cent. of alcoholic extract of belladonna. _Alcoholic Extract of
Belladonna._--This extract, according to Squire,[487b] contains from 1·6
to 4·45 per cent. of alkaloid. _Belladonna liniment_ is an alcoholic
extract with the addition of camphor; its strength is about equal to 0·2
per cent. of alkaloid. _Belladonna ointment_ contains about 10 per cent.
of the alcoholic extract.
[487b] _Companion to the British Pharmacopœia_, 1894.
(_c._) _The Alkaloid.--Atropine Discs_ (_lamellæ atropinæ_).--These are
discs of gelatin, each weighing about 1/50 grain, and containing for
ophthalmic use 1/5000 grain of atropine sulphate. Similar discs are made
for hypodermic use, but stronger; each containing 1/120 grain. _Solution
of Atropine Sulphate._--Strength about 1 per cent. _Atropine
Ointment._--Strength about 1 in 60, or 1·60 per cent. of atropine.
(_d._) _Stramonium._--An extract of the seeds is officinal in Britain;
the alkaloidal content is from 1·6 to 1·8 per cent. There is also a
tincture which contains about 0·06 per cent. of alkaloid.
§ 444. =Properties of Atropine=, C₁₇H₂₃NO₃.--Atropine, hyoscyamine, and
hyoscine have all the same formula, but differ in their molecular
constitution. Atropine by hydrolysis, either by heating it with
hydrochloric acid or baryta water, is decomposed into tropine and tropic
acid:--
C₁₇H₂₃NO₃ + H₂O = C₈H₁₅NO + C₉H₁₀O₃.
Atropine. Tropine. Tropic
acid.
On the other hand, by heating tropic acid and tropine together,
atropine is regenerated. Hence it is proved by analysis and
synthesis, that atropine is tropic acid-tropine, just as aconitine is
benzoyl-aconine. Tropic acid has been produced synthetically by
boiling β-chlorphenyl-propionic acid with potash, which at once shows
its constitutional formula, viz.:--
CH₂OH
/
C₆H₅CH .
\
COOH
Tropic acid has a melting-point of 117° to 118°. Tropine is a four-fold
hydrated oxethyl-methyl-pyridine, and has the constitutional formula of
C₅H₃(H₄)(C₂H₄OH)N(CH₃); hence the constitutional formula of atropine
is--
CH₂(OH)
/
C₆H₅--CH .
\
CO--O(C₂H₄--C₅H₇==N--CH₃)
Tropine is a white, crystalline, strongly alkaline mass, melting at 60°,
and volatilising at 230° undecomposed. It is soluble in water, alcohol,
and ether, and gives precipitates with tannic acid, iodised hydriodic
acid, Mayer’s reagent, gold chloride, and mercuric chloride. Tropine
gold chloride melts at 210° to 212°. Atropic acid (C₉H₈O₂),
melting-point 198° to 200°, and isatropic acid (C₉H₈O₂), may also be
obtained by the action of hydrochloric acid--the first, in radiating
crystals, melting at 106°, and capable of distillation; the second, in
thin rhombic plates, melting about 200°, and not volatile. Picric acid
also gives a precipitate of beautiful plates. To obtain this the
carbazotic acid must be in excess, and time must be given for the
precipitate to form.
Atropine forms colourless crystals (mostly in groups or tufts of needles
and prisms), which are heavier than water, and possess no smell, but an
unpleasant, long-enduring, bitter taste. The experiments of E. Schmidt
place the melting-point between 115° and 115·5°. It is said to sublime
scantily in a crystalline form, but the writer has been unable to obtain
any crystals by sublimation; faint mists collect on the upper disc, at
about 123°, but they are perfectly amorphous.
Its reaction is alkaline; one part requires, of cold water, 300; of
boiling, 58; of ether, 30; of benzene, 40; and of chloroform, 3 parts
for solution. In alcohol and amyl alcohol it dissolves in almost every
proportion. It turns the plane of polarisation weakly to the left.
§ 445. =Tests.=--Atropine mixed with nitric acid exhibits no change of
colour. The same is the case with concentrated sulphuric acid in the
cold; but on heating, there ensues the common browning, with development
of a peculiar odour, likened by Gulielmo to orange flowers, by
Dragendorff to the flowers of the _Prunus padus_, and by Otto to the
_Spiræa ulmaria_--a sufficient evidence of the untrustworthiness of this
as a distinctive test. The odour, indeed, with small quantities, is
certainly not powerful, nor is it strongly suggestive of any of the
plants mentioned. A far more intense odour is given off if a speck of
atropine is evaporated to dryness with a few drops of strong solution of
baryta, and heated strongly; the scent is decidedly analogous to that of
hawthorn-blossom, and unmistakably agreeable.
By boiling a small quantity of atropine, say 1 mgrm., with 2 mgrms. of
calomel and a very little water, the calomel blackens, and crystals may
be obtained of a double salt; this reaction is, however, given also by
hyoscyamine and homatropine. Mercuric potassium iodide solution, and
mercuric bromide solution give amorphous precipitates, which, after a
time, become crystalline, and have characteristic forms.
A solution of iodine in potassium iodide gives a precipitate with
acidulated solutions of atropine in even a dilution of 1 : 10,000.
Tannin precipitates, and the precipitate is soluble in excess of the
reagent. If atropine be dissolved in dilute hydrochloric acid, and a 5
per cent. of gold chloride solution be added, a precipitate of a gold
compound (C₁₇H₂₃NO₃HClAuCl₃) separates. The precipitate is in the form
of rosettes or needles; melting-point 137°. On boiling it with water,
however, it melts into oily drops, and this peculiar behaviour
distinguishes it from the analogous salt of hyoscyamine, which does not
melt in boiling water. The percentage of gold left on a combustion of
atropine gold chloride is 31·35 per cent. 100 parts of the gold salt are
equal to 46·2 of atropine. A platinum salt may also be obtained,
(C₁₇H₂₃NO₃HCl)₂,PtCl₄, containing 29·5 per cent. of platinum.
Vitali’s test is important; it consists in the production of a violet
colour with alcoholic potash after oxidation.
The test may be applied as follows:--Equal parts, say 1 mgrm., of
nitrate of sodium and of the substance to be tested, are rubbed together
with a glass rod on a porcelain slab, and to this mixture 1 drop of
sulphuric acid is added; the mixture is spread out in a thin film; upon
this is strewn a little powdered potassium hydrate, and finally 1 drop
of alcohol added; a violet colour is produced which passes into a fine
red; according to the author of the test, 0·001 mgrm. of atropine
sulphate can by this test be detected. Strychnine obscures this
reaction.
Atropine, homatropine, and hyoscyamine show an alkaline reaction with
phenolphthalein: atropine and homatropine give a precipitate with HgCl₂.
Hyoscyamine, not cocaine, precipitates HgCl₂, and is alkaline to litmus,
but not to phenolphthalein. Atropine behaves as follows:--(1) Sodium
nitrate, sulphuric acid, and afterwards sodium hydroxide, gives a violet
colour; (2) the test as before, but with nitrite instead of nitrate,
gives orange colour, which, on dilution with sodium hydroxide solution,
changes to red, violet, or lilac; (3) when heated with glacial acetic
acid and sulphuric acid for a sufficient time, a greenish-yellow
fluorescence is produced.--_Flückiger, Pharm. Journ. Trans._ (3), vol.
xvi. p. 601-602.
The two alkaloids, strychnine and atropine, are not likely to be often
together in the human body, but that it may sometimes occur is shown by
a case recorded by L. Fabris.[488] A patient in the hospital at Padua
had for some time been treated with daily injections of 3 mgrms. of
strychnine nitrate; unfortunately, one day, instead of the 3 mgrms. of
strychnine, the same quantity of atropine sulphate was injected, and the
patient died after a few hours, with symptoms of atropine poisoning.
[488] _Gazzetta_, xxii., i. 347-350.
On chemical treatment of the viscera, a mixture of alkaloids was
obtained which did not give either the reactions of strychnine or of
atropine. To test the possibility of these alkaloids obscuring each
other’s reactions, mixtures of 3 per cent. solutions (the strength of
the injections) of atropine sulphate and strychnine nitrate were mixed
together, and strychnine tested for by the dichromate and sulphuric acid
test.
A mixture of equal parts gave the strychnine reaction very clearly, but
the atropine reaction not at all; 1 strychnine with 3 of atropine gave
strychnine reaction, but not that of atropine; 1 strychnine with 4
atropine gave indistinct reaction for both alkaloids; 1 of strychnine
with 5 of atropine gave a momentary atropine reaction, the violet was,
however, almost immediately replaced by a red colour. Vitali’s reaction
was not clearly shown until the mixture was in the proportion of 9 of
atropine to 1 of strychnine, but mixtures in the proportion of 3
strychnine and 1 atropine will give distinct mydriasis.
In such a case, of course, the strychnine should be separated from the
atropine; this can be effected by precipitating the strychnine as
chromate, filtering and recovering from the filter the atropine by
alkalising and shaking it out with ether.
The atropine may be farther purified by converting it into oxalate,
dissolving the oxalate in as small a quantity of alcohol as possible,
and precipitating the oxalate out with ether; the precipitate is
collected, dissolved in as small a quantity of water as possible, the
water made alkaline, and the base shaken out with ether.
The most reliable test for atropine, or one of the mydriatic alkaloids,
is its action on the iris; a solution of atropine, even so weak as 1 :
130,000, causing dilatation.[489] This action on the iris has been
studied by Ruyter,[490] Donders, and von Graefe.
[489] _De Actione Atropæ Belladonnæ in Iridem_, Traj. ad Rhen., 1852.
[490] _Arch. Ophthal._, ix. 262, 1864.
The action is local, taking effect when in dilute solution only on the
eye to which it has been applied; and it has been produced on the eyes
of frogs, not only in the living subject, but after the head has been
severed from the body and deprived of brain. The thinner the cornea, the
quicker the dilatation; therefore, the younger the person or animal, the
more suitable for experiment. In frogs, with a solution of 1 : 250,
dilatation commences in about five minutes; in pigeons, seven minutes;
and in rabbits, ten minutes. In man, a solution of 1 : 120 commences to
act in about six to seven minutes, reaches its highest point in from ten
to fifteen minutes, and persists more or less for six to eight days. A
solution of 1 : 480 acts first in fifteen to twenty minutes, and reaches
its greatest point in twenty minutes; a solution of 1 : 48,000 requires
from three-quarters of an hour to an hour to show its effect. Dogs and
cats are far more sensible to its influence than man, and therefore more
suitable for experiment. If the expert chooses, he may essay the proof
upon himself, controlling the dilatation by Calabar bean; but it is
seldom necessary or advisable to make personal trials of this
nature.[491]
[491] A. Ladenburg (_Compt. Rend._, xc. 92), having succeeded in
reproducing atropine by heating tropine and tropic acid with
hydrochloric acid, by substituting various organic acids for the tropic
acid, has obtained a whole series of compounds to which he has given the
name of _tropeines_. One of these, hydroxytoluol (amygdalic) tropeine,
he has named _homatropine_. It dilates the pupil, but is less poisonous
than atropine.
§ 446. =Statistics of Atropine Poisoning.=--Since atropine is the active
principle of belladonna and datura plants, and every portion of
these--root, seeds, leaves, and fruit--has caused toxic symptoms,
poisoning by any part of these plants, or by their pharmaceutical or
other preparations, may be considered with strict propriety as atropine
poisoning. Our English death statistics for the ten years ending 1892,
record 79 deaths (50 males and 29 females) from atropine (for the most
part registered under the head of belladonna); 29 (or 36·7 per cent.)
were suicidal, the rest accidental.
The greatest number of the accidental cases arise from mistakes in
pharmacy; thus, belladonna leaves have been supplied for ash leaves; the
extract of belladonna has been given instead of extract of juniper; the
alkaloid itself has been dispensed in mistake for theine;[492] a more
curious and marvellously stupid mistake is one in which it was dispensed
instead of assafœtida (Schauenstein, _op. cit._, p. 652). Further,
valerianate of atropine has been accidentally substituted for quinine
valerianate, and Schauenstein relates a case in which atropine sulphate
was administered subcutaneously instead of morphine sulphate; but the
result was not lethal. Many other instances might be cited. The extended
use of atropine as an external application to the eye naturally gives
rise to a few direct and indirect accidents. Serious symptoms have
arisen from the solution reaching the pharynx through the lachrymal duct
and nose. A curious indirect poisoning, caused by the use of atropine as
a collyrium, is related by Schauenstein.[493] A person suffered from all
the symptoms of atropine poisoning; but the channel by which it had
obtained access to the system was a great mystery, until it was traced
to some coffee, and it was then found that the cook had strained this
coffee through a certain piece of linen, which had been used months
before, soaked in atropine solution, as a collyrium, and had been cast
aside as of no value.
[492] Hohl, _De Effectu Atropini. Diss. Halle_, 1863.
[493] Maschka’s _Handbuch_.
§ 447. =Accidental and Criminal Poisoning by Atropine.=--External
applications of atropine are rapidly absorbed, _e.g._, if the foot of a
rat be steeped for a little while in a solution of the alkaloid, and the
eyes watched, dilatation of the pupils will soon be observed. If the
skin is broken, enough may be absorbed to cause death. A case is on
record in which ·21 grm. of atropine sulphate, applied as an ointment to
the abraded skin, was fatal.[494] Atropine has also been absorbed from
the bowel; in one case, a clyster containing the active principles of
5·2 grms. (80 grains) of belladonna root was administered to a woman
twenty-seven years of age, and caused death. Allowing the root to have
been carefully dried, and to contain ·21 per cent. of alkaloid, it would
seem that so little as 10·9 mgrms. (·16 grain) may even prove fatal, if
left in contact with the intestinal mucous membrane. Belladonna berries
and stramonium leaves and seeds are eaten occasionally by children. A
remarkable series of poisonings by belladonna berries occurred in London
during the autumn of 1846.
[494] Ploss, _Zeitschr. f. Chir._, 1863.
Criminal poisoning by atropine in any form is of excessive rarity in
Europe and America, but in India it has been frightfully prevalent. In
all the Asiatic cases the substance used has been one of the various
species of datura, and mostly the bruised or ground seeds, or a
decoction of the seeds. In 120 cases recorded in papers and works on
Indian toxicology, I find no less than 63 per cent. of the cases
criminal, 19 per cent. suicidal, and 18 per cent. accidental. In noting
these figures, however, it must be borne in mind that known criminal
cases are more certain to be recorded than any other cases. The drug has
been known under the Sanscrit name of _dhatoora_ by the Hindoos from
most remote times. It was largely used by the Thugs, either for the
purpose of stupefying their victim or for killing him; by loose wives to
ensure for a time the fatuity of their husbands; and, lastly, it seems
in Indian history to have played the peculiar _rôle_ of a state agent,
and to have been used to induce the idiocy or insanity of persons of
high rank, whose mental integrity was considered dangerous by the despot
in power. The Hindoos, by centuries of practice, have attained such
dexterity in the use of the “datura” as to raise that kind of poisoning
to an art, so that Dr. Chevers, in his _Medical Jurisprudence for
India_,[495] declares that “there appears to be no drug known in the
present day which represents in its effects so close an approach to the
system of slow poisoning, believed by many to have been practised in the
Middle Ages, as does the datura.”
[495] Dr. Chevers’s work contains a very good history of datura criminal
poisoning.
§ 448. =Fatal Dose.=--It is impossible to state with precision the exact
quantity which may cause death, atropine being one of those substances
whose effect, varying in different cases, seems to depend on special
constitutional tendencies or idiosyncracies of the individual. Some
persons take a comparatively large amount with impunity, while others
scarcely bear a very moderate dose without exhibiting unpleasant
symptoms. Eight mgrms. (⅛ grain) have been known to produce poisonous
symptoms, and ·129 grm. (2 grains) death. We may, therefore, infer that
about ·0648 grm. (1 grain) would, unchecked by remedies, probably act
fatally; but very large doses have been recovered from, especially when
treatment has been prompt.
Atropine is used in veterinary practice, from 32·4 to 64·8 mgrms. (½ to
1 grain) and more being administered subcutaneously to horses; but the
extent to which this may be done with safety is not yet established.
§ 449. =Action on Animals.=--The action of atropine has been studied on
certain beetles, on reptiles (such as the salamander, triton, frogs, and
others), on guinea-pigs, hedgehogs, rats, rabbits, fowls, pigeons, dogs,
and cats. Among the mammalia there is no essential difference in the
symptoms, but great variation in the relative sensibility; man seems the
most sensitive of all, next to man come the carnivora, while the
herbivora, and especially the rodents, offer a considerable resistance.
According to Falck the lethal dose for a rabbit is at least ·79 mgrm.
per kilo. It is the general opinion that rabbits may eat sufficient of
the belladonna plant to render their flesh poisonous, and yet the
animals themselves may show no disturbance in health; but this must not
be considered adequately established. Speaking very generally, the
higher the animal organisation the greater the sensibility to atropine.
Frogs are affected in a peculiar manner. According to the researches of
Fraser,[496] the animal is first paralysed, and some hours after the
administration of the poison lies motionless, the only signs of life
being the existence of a slight movement of the heart and muscular
irritability. After a period of from forty-eight to seventy-two hours,
the fore limbs are seized with tetanic spasms, which develop into a
strychnine-like tetanus.
[496] _Transact. of Edin. Roy. Soc._, vol. xxv. p. 449. _Journ. of Anat.
and Physiol._, May 1869, p. 357.
§ 450. =Action on Man.=--When atropine is injected subcutaneously, the
symptoms, as is usually the case with drugs administered in this manner,
may come on immediately, the pupil not unfrequently dilating almost
before the injection is finished. This is in no way surprising; but
there are instances in which decoctions of datura seeds have been
administered by the stomach, and the commencement of symptoms has been
as rapid as in poisoning by oxalic or even prussic acid. In a case tried
in India in July 1852, the prosecutor declared that, while a person was
handing him a _lota_ of water, the prisoner snatched it away on pretence
of freeing the water from dirt or straws, and then gave it to him. He
then drank only two mouthfuls, and, complaining of the bitter taste,
fell down insensible within forty yards of the spot where he had drunk,
and did not recover his senses until the third day after. In another
case, a man was struck down so suddenly that his feet were scalded by
some hot water which he was carrying.--_Chevers._
When the seeds, leaves, or fruit of atropine-holding plants are eaten,
there is, however, a very appreciable period before the symptoms
commence, and, as in the case of opium poisoning, no very definite rule
can be laid down, but usually the effects are experienced within half
an hour. The first sensation is dryness of the mouth and throat; this
continues increasing, and may rise to such a degree that the swallowing
of liquids is an impossibility. The difficulty in swallowing does not
seem to be entirely dependent on the dry state of the throat, but is
also due to a spasmodic contraction of the pharyngeal muscles.
Tissore[497] found in one case such constriction that he could only
introduce emetics by passing a catheter of small diameter. The mucous
membrane is reddened, and the voice hoarse.[498] The inability to
swallow, and the changed voice, bear some little resemblance to
hydrophobia--a resemblance heightened to the popular mind by an
inclination to bite, which seems to have been occasionally observed; the
pupils are early dilated, and the dilatation may be marked and extreme;
the vision is deranged, letters and figures often appear duplicated; the
eyeballs are occasionally remarkably prominent, and generally congested;
the skin is dry, even very small quantities of atropine arresting the
cutaneous secretion; in this respect atropine and pilocarpine are
perfect examples of antagonism. With the dryness of skin, in a large
percentage of cases, occurs a scarlet rash over most of the body. This
is generally the case after large doses, but Stadler saw the rash
produced on a child three months old by ·3 mgrm. of atropine sulphate.
It appeared three minutes after the dose, lasted five hours, and was
reproduced by a renewed dose.[499] The temperature of the body with
large doses is raised; with small, somewhat lowered. The pulse is
increased in frequency, and is always above 100--mostly from 115 to 120,
or even 150, in the minute. The breathing is at first a little slowed,
and then very rapid. Vomiting is not common; the sphincters may be
paralysed so that the evacuations are involuntary, and there may be also
spasmodic contractions of the urinary bladder. The nervous system is
profoundly affected; in one case there were clonic spasms,[500] in
another,[501] such muscular rigidity, that the patient could with
difficulty be placed on a chair. The lower extremities are often partly
paralysed, there is a want of co-ordination, the person reels like a
drunken man, or there may be general jactitation. The disturbance of
the brain functions is very marked; in about 4 per cent. only of the
recorded cases has there been no delirium, or very little--in the
majority delirium is present. In adults this generally takes a
garrulous, pleasing form, but every variety has been witnessed. Dr. H.
Giraud describes the delirium from datura (which it may be necessary to
again repeat is _atropine_ delirium) as follows:--“He either vociferates
loudly or is garrulous, and talks incoherently; sometimes he is
mirthful, and laughs wildly, or is sad and moans, as if in great
distress; generally he is observed to be very timid, and, when most
troublesome and unruly, can always be cowed by an angry word, frequently
putting up his hands in a supplicating posture. When approached he
suddenly shrinks back as if apprehensive of being struck, and frequently
he moves about as if to avoid spectra. But the most invariable
accompaniment of the final stage of delirium, and frequently also that
of _sopor_, is in the incessant picking at real or imaginary objects. At
one time the patient seizes hold of parts of his clothes or bedding,
pulls at his fingers and toes, takes up dirt and stones from the ground,
or as often snatches at imaginary objects in the air, on his body, or
anything near him. Very frequently he appears as if amusing himself by
drawing out imaginary threads from the ends of his fingers, and
occasionally his antics are so varied and ridiculous, that I have seen
his near relatives, although apprehensive of danger, unable to restrain
their laughter.”[502] This active delirium passes into a somnolent state
with muttering, catching at the bedclothes, or at floating spectra, and
in fatal cases the patient dies in this stage. As a rule, the sleep is
not like opium coma; there is complete insensibility in both, but in the
one the sleep is deep, without muttering, in the other, from atropine,
it is more like the stupor of a fever. The course in fatal cases is
rapid, death generally taking place within six hours. If a person live
over seven or eight hours, he usually recovers, however serious the
symptoms may appear. On waking, the patient remembers nothing of his
illness; mydriasis remains some time, and there may be abnormality of
speech and weakness of the limbs, but within four days health is
re-established. In cases where the seeds have been swallowed, the
symptoms may be much prolonged, and they seem to continue until all the
seeds have been voided--perhaps this is due to the imperfect but
continuous extraction of atropine by the intestinal juices.
[497] _Gaz. hebd._, 1856.
[498] A friend of the author’s was given, by a mistake in dispensing, 16
minims of a solution of atropine sulphate, equivalent to 1/7 grain of
atropine (or 9·3 mgrms). Ten minutes after taking the dose there was
dilatation of the pupil, indistinctness of vision, with great dryness of
the throat and difficulty in swallowing; he attempted to eat a biscuit,
but, after chewing it, he was obliged to spit it out, as it was not
possible to swallow; the throat was excessively sore, and there was a
desire to pass urine, but only a few drops could be voided. In
forty-five minutes he was unable to stand or walk. There was a bright
rash on the chest. In two hours he became insensible, and was taken to
the Middlesex Hospital, recovering under treatment in about eight hours.
[499] _Med. Times_, 1868.
[500] _Lancet_, vol. i., 1881, p. 414.
[501] _Ibid._, vol. i., 1876, p. 346.
[502] In an English case of belladonna poisoning, the patient, a tailor,
sat for four hours, moving his hands and arms as if sewing, and his lips
as if talking, but without uttering a word.
Chronic poisoning by atropine may, from what has been stated, be of
great importance in India. It is probable that its continuous effect
would tend to weaken the intellect, and there is no reason for any
incredulity with regard to its power as a factor of insanity. Rossbach
has ascertained that if dogs are, day after day, dosed with atropine,
they become emaciated; but a certain tolerance is established, and the
dose has to be raised considerably after a time to produce any marked
physiological effect.
§ 451. =Physiological Action of Atropine.=--From the numerous
experiments on animals which have been performed for the purpose of
elucidating the action of atropine, it is clear that the terminations of
the vagus in the heart muscle are first excited, and then paralysed. The
excitor-motor ganglion is also paralysed, and finally the heart itself;
death resulting from heart paralysis. The respiratory disturbance is
also to be ascribed to the vagus; the terminations in the lung are
paralysed, and, at the same time, the poison circulating through the
respiratory nervous centre stimulates it first, and then it also becomes
finally paralysed. The small vessels are generally widened after a
previous transitory narrowing. Organs containing unstriped muscular
fibre are generally paralysed, as well as the ends of the nerves
regulating secretion--hence the dryness of the skin. The action on the
iris is not thoroughly elucidated.
§ 452. The _diagnosis_ of atropine poisoning may be very difficult
unless the attention of the medical man be excited by some suspicious
circumstance. A child suffering from belladonna rash, with hot dry skin,
quick pulse, and reddened fauces, looks not unlike one under an attack
of scarlet fever. Further, as before mentioned, some cases are similar
to rabies; and again, the garrulous delirium and the hallucinations of
an adult are often very similar to those of _delirium tremens_, as well
as tomania.
§ 453. =Post-mortem Appearances.=--The _post-mortem_ appearances do not
seem to be characteristic, save in the fact that the pupils remain
dilated. The brain is usually hyperæmic, and in one case the absence of
moisture seems to have been remarkable. The stomach and intestines may
be somewhat irritated if the seeds, leaves, or other parts of the plant
have been eaten; but the irritation is not constant if the poisoning has
been by pure atropine, and still less is it likely to be present if
atropine has been administered subcutaneously.
§ 454. =Treatment.=--The great majority of cases recover under
treatment. In 112 cases collected by F. A. Falck, 13 only were fatal
(11·6 per cent.). The greater portion of the deaths in India are those
of children and old people--persons of feeble vitality. The Asiatic
treatment, which has been handed down by tradition, is the application
of cold water to the feet; but the method which has found most favour in
England is treatment by pilocarpine, a fifth of a grain or more being
injected from time to time. Pilocarpine shows as perfect antagonism as
possible; atropine dries, pilocarpine moistens the skin; atropine
accelerates, pilocarpine slows the respiration. Dr. Sydney Ringer and
others have published a remarkable series of cases showing the efficacy
of this treatment, which, of course, is to be combined where necessary
with emetics, the use of the stomach-pump, &c.[503]
[503] See, for Dr. Ringer’s cases, _Lancet_, vol. i., 1876, p. 346.
Refer also to _Brit. Med. Journ._, vol. i., 1881, p. 594; _ib._, p. 659.
§ 455. =Separation of Atropine from Organic Tissues, &c.=--From the
contents of the stomach, atropine may be separated by acidulating
strongly with sulphuric acid (15 to 20 c.c. of dilute H₂SO₄ to 100
c.c.), digesting for some time at a temperature not exceeding 70°, and
then reducing any solid matter to a pulp by friction, and filtering,
which can generally be effected by the aid of a filter-pump. The liver,
muscles,[504] and coagulated blood, &c., may also be treated in a
precisely similar way. The acid liquid thus obtained, is first, to
remove impurities, shaken up with amyl alcohol, and after the separation
of the latter in the usual manner, it is agitated with chloroform, which
will take up any of the remaining amyl alcohol,[505] and also serve to
purify further. The chloroform is then removed by a pipette (or the
separating flask before described), and the fluid made alkaline, and
shaken up with ether, which, on removal, is allowed to evaporate
spontaneously. The residue will contain atropine, and this may be
farther purified by converting it into oxalate, as suggested, page 374.
[504] Neither amyl alcohol nor chloroform removes atropine from an
_acid_ solution.
[505] Atropine goes into the blood, and appears to be present in the
different organs in direct proportion to the quantity of blood they
contain. Dragendorff has found in the muscles of rabbits fed upon
belladonna sufficient atropine for quantitative estimation.
From the urine,[506] atropine may be extracted by acidifying with
sulphuric acid, and agitation with the same series of solvents. Atropine
has been separated from putrid matters long after death, nor does it
appear to suffer any decomposition by the ordinary analytical operations
of evaporating solutions to dryness at 100°. In other words, there seems
to be no necessity for operations _in vacuo_, in attempts at separating
atropine.
[506] Dragendorff has found atropine in the urine of rabbits fed with
belladonna; the separation by the poison is so rapid that it often can
only be recognised in the urine during the first hour after the poison
has been taken.
TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE HENBANE
PLANT.
+----------------------------+-------+-------+-------+-------+
| | Seeds,|Leaves,| Stalk,| Root, |
+----------+---------+-------+-------+-------+-------+-------+
| Plant | Hyosc.- | 1868. | ... | 0·588 | 0·012 | 0·128 |
| Desti- | Albus. | 1869. | ... | 0·469 | ... | 0·176 |
| tute +---------+-------+-------+-------+-------+-------+
| of | Hyosc.- | 1868. | ... | 0·154 | 0·070 | 0·027 |
| Flowers. | Niger. | 1869. | ... | 0·192 | 0·017 | 0·080 |
+----------+---------+-------+-------+-------+-------+-------+
| | Hyosc.- | 1868. | ... | 0·359 | 0·036 | 0·146 |
| Plant | Albus. | 1869. | ... | 0·329 | 0·048 | 0·262 |
| in +---------+-------+-------+-------+-------+-------+
| Flower. | Hyosc.- | 1868. | ... | 0·147 | 0·032 | 0·127 |
| | Niger. | 1869. | ... | 0·206 | 0·030 | 0·138 |
+----------+---------+-------+-------+-------+-------+-------+
| | Hyosc.- | 1868. | 0·162 | 0·211 | 0·027 | 0·106 |
| Plant | Albus. | 1869. | 0·172 | 0·153 | 0·029 | 0·086 |
| in +---------+-------+-------+-------+-------+-------+
| Fruit. | Hyosc.- | 1868. | 0·075 | 0·065 | 0·009 | 0·028 |
| | Niger. | 1869. | 0·118 | 0·110 | 0·010 | 0·056 |
+----------+---------+-------+-------+-------+-------+-------+
2. HYOSCYAMINE.
§ 456. This powerful alkaloid is contained in small quantities in datura
and belladonna, and also is found in the common lettuce (·001 per
cent.),[507] and in _Scopola carmolica_, a solanaceous plant
indigenous to Austria and Hungary[508]; but its chief source is the
_Hyoscyamus niger_ and _Hyoscyamus alba_ (black and white henbane): it
is also found in the _Duboisia myoporoides_. The latter plant was
considered to contain a new alkaloid, “_Duboisine_,” but duboisine is a
mixture of hyoscyamine and hyoscine. Ladenburg’s hyoscine accompanies
hyoscyamine, and is an isomeride of both atropine and hyoscyamine; its
chemical reactions are similar to those of hyoscyamine, as well as its
physiological effects.[509]
[507] T. S. Dymond, _Journ. Chem. Soc. Trans._, 1892, 90.
[508] W. R. Dunstan and A. E. Chaston. _Pharm. Journ. Trans._ (3), xx.
461-464.
[509] See _Ber. der deutsch. Chem. Gesell._, 13, 1549 to 1554. By
boiling hyoscine hydrochloride with animal charcoal, and then
precipitating with auric chloride, a good crystalline compound, melting
at 198°, can be obtained.
=Hyoscyamine= (C₁₇H₂₃NO₃), as separated in the course of analysis, is a
resinoid, sticky, amorphous mass, difficult to dry, and possessing a
tobacco-like odour. It can, however, be obtained in well-marked
odourless crystals, which melt at 108°-109°, a portion subliming
unchanged. It liquefies under boiling water without crystallisation.
According to Thorey,[510] hyoscyamine crystallises out of chloroform in
rhombic tables, and out of benzene in fine needles; but out of ether or
amyl alcohol it remains amorphous. When perfectly pure, it dissolves
with difficulty in cold, but more readily in hot, water; if impure, it
is hygroscopic, and its solubility is much increased. In any case, it
dissolves easily in alcohol, ether, chloroform, amyl alcohol, benzene,
and dilute acids. Hyoscyamine neutralises acids fully, and forms
crystallisable salts, which assume for the most part the form of
needles. It is isomeric with atropine, and is converted into atropine by
heating to 110°, or warming with alcoholic potash. The gold salt melts
at 159°, and does not melt in boiling water like the atropine gold salt.
[510] _Pharm. Zeitschr. f. Russl._, 1869.
§ 457. =Pharmaceutical and other Preparations of Henbane.=--The leaves
are alone officinal in the European pharmacopœias; but the seeds and the
root, or the flowers, may be met with occasionally, especially among
herbalists. The table[511] (p. 382) will give an idea of the alkaloidal
content of the different parts of the plant.
[511] This table, taken from Dragendorff’s _Chemische Werthbestimmung
einiger starkwirkenden Droguen_, embodies the researches of Thorey.
In order to ascertain the percentage of the alkaloid in any part of the
plant, the process followed by Thorey has the merit of simplicity. The
substance is first exhausted by petroleum ether, which frees it from
fat; after drying, it is extracted with 85 per cent. alcohol at a
temperature not exceeding 40°. The alcoholic extracts are then united,
the alcohol distilled off, and the residue filtered. The filtrate is now
first purified by agitation with petroleum ether, then saturated by
ammonia, and shaken up with chloroform. The latter, on evaporation,
leaves the alkaloid only slightly impure, and, after washing with
distilled water, if dissolved in dilute sulphuric acid, a crystalline
sulphate may be readily obtained.
=A tincture and an extract of henbane leaves and flowering tops= are
officinal in most pharmacopœias; an extract of the seeds in that of
France.
=An oil of hyoscyamus= is officinal in all the Continental
pharmacopœias, but not in the British.
=Henbane juice= is recognised by the British pharmacopœia; it is about
the same strength as the tincture.
=An ointment=, made of one part of the extract to nine of simple
ointment, is officinal in the German pharmacopœia.
The tincture (after distilling off the spirit) and the extracts (on
proper solution) may be conveniently titrated by Mayer’s reagent (p.
263), which, for this purpose, should be diluted one-half; each c.c.
then, according to Dragendorff, equalling 6·98 mgrms. of hyoscyamine.
Kruse found 0·042 per cent. of hyoscyamine in a Russian tincture, and
·28 per cent. in a Russian extract. Any preparation made with extract of
henbane will be found to contain nitrate of potash, for Attfield has
shown the extract to be rich in this substance. The ointment will
require extraction of the fat by petroleum ether; this accomplished, the
determination of its strength is easy.
=The oil of hyoscyamus= is poisonous, and contains the alkaloid. An
exact quantitative research is difficult; but if 20 grms. of the oil are
shaken up for some time with water acidified by sulphuric acid, the
fluid separated from the oil, made alkaline, shaken up with chloroform,
and the latter removed and evaporated, sufficient will be obtained to
test successfully for the presence of the alkaloid, by its action on the
pupil of the eye.
§ 458. =Dose and Effects.=--The dose of the uncrystalline hyoscyamine is
6 mgrms. (1/10 grain), carefully increased. I have seen it extensively
used in asylums to calm violent or troublesome maniacs. Thirty-two
mgrms. (½ grain) begin to act within a quarter of an hour; the face
flushes, the pupils dilate, there is no excitement, all muscular motion
is enfeebled, and the patient remains quiet for many hours, the effects
from a single dose not uncommonly lasting two days. 64·8 mgrms. (1
grain) would be a very large, and possibly fatal, dose. The absence of
delirium or excitement, with full doses of hyoscyamine, is a striking
contrast to the action of atropine, in every other respect so closely
allied; yet there are cases on record showing that the henbane root
itself has an action similar to that of belladonna, unless indeed one
root has been mistaken for another; _e.g._, Sonnenschein relates the
following ancient case of poisoning:--In a certain cloister the monks
ate by error the root of henbane. In the night they were all taken with
hallucinations, so that the pious convent was like a madhouse. One monk
sounded at midnight the matins, some who thereupon came into chapel
could not read, others read what was not in the book, others sang
drinking songs--in short, there was the greatest disturbance.
§ 459. =Separation of Hyoscyamine from Organic Matters.=--The isolation
of the alkaloid from organic tissues or fluids, in cases where a
medicinal preparation of henbane, or of the leaves, root, &c., has been
taken, is possible, and should be carried out on the principles already
detailed. Hyoscyamine is mainly identified by its power of dilating the
pupil of the eye. It is said that so small a quantity as ·0083 mgrm.
(1/4000 grain) will in fifteen minutes dilate the eye of a rabbit. It is
true that atropine also dilates the pupil; but if sufficient of the
substance should have been isolated to apply other tests, it can be
distinguished from atropine by the fact that the latter gives no
immediate precipitate with platinic chloride, whilst hyoscyamine is
precipitated by a small quantity of platinic chloride, and dissolved by
a larger amount, and also by the characters of the gold salt.
3. HYOSCINE.
§ 460. =Hyoscine=, C₁₇H₂₃NO₃.--According to E. Schmidt[512] the
formula is C₁₇H₂₁NO₄ + H₂O, and the alkaloid is identical with
scopolamine. Scopolamine has a m.p. of 59°, gives an aurochloride,
crystallising in needles, the m.p. of which is 212° to 214°; when
boiled with baryta water, it splits up into atropic acid and
scopoline, a base (C₈H₁₃NO), m.p. 110°, boiling-point, 241° to 243°;
scopoline forms an aurochloride, m.p. 223°-225°; and a
platinochloride, m.p. 228°-230°; but Ladenburg,[513] in answer to
Schmidt, asserts that hyoscine exists, and is not identical with
scopolamine. A sample of commercial hyoscine hydrobromide Nagelvoort
found to melt, water-free, at 198°; other commercial samples of
hydrobromide melted at 179° and 186°; the latter sample giving an
aurochloride which melted at 192°. Pure hyoscine gold chloride is
stated to melt at 198°. Its reactions are much the same as those of
atropine, but it does not blacken calomel. It is very poisonous.
[512] _Arch. Pharm._, ccxxx. 207-231.
[513] _Ber._, xxv. 2388-2394.
According to experiments on animals, the heart is first slowed, then
quickened; the first effect being due to a stimulation of the
inhibitory nervous apparatus, the second to a paralysing action on
the same. The temperature is not altered. The pupils are dilated,
the saliva diminished. The irritability of the brain is
lessened.[514]
[514] Parloff, _St Petersburg Med. Chem. Acad._, Dissert. No. 9,
1889-90.
4. SOLANINE.
§ 461. =Distribution of Solanine.=--Solanine is a poisonous
nitrogenised glucoside found in all parts of the plants belonging to
the nightshade order. The English common plants in which solanine
occurs are the edible potato plant (_Solanum tuberosum_), the
nightshade (_Solanum nigrum_), and the _Solanum dulcamara_, or
bitter-sweet. The berries of the _Solanum nigrum_ and those of _S.
dulcamara_ contain about 0·3 per cent. Mature healthy potatoes
appear to contain no solanine, but from 150 grms. of diseased
potatoes G. Kassner[515] separated 30 to 50 mgrms.
[515] _Arch. Pharm._ (3), xxv. 402, 403.
R. Firbas,[516] in a research on the active substances or young
shoots of the _S. tuberosum_ found two products--one crystalline,
_Solanine_; the other amorphous, _Solaneine_. He gives the following
formula to solanine--C₅₂H₉₃NO₁₈4½H₂O; when dried at 100° it becomes
anhydrous. From a solution in 85 per cent. alcohol it crystallises
in colourless needles, m.p. 244°; these are almost insoluble in
ether and alcohol, but are readily dissolved in dilute hydrochloric
acid. On hydrolysis solanine breaks up into solanidine and a sugar,
according to the equation--
[516] _Monatsh._, x. 541-560; _Journ. Chem. Soc._ (Abst.), Jan. 1890.
C₅₂H₉₃NO₁₈ = C₄₀H₆₁NO₂ + 2C₆H₁₂O₆ + 4H₂O.
§ 462. =Properties of Solanine.=--The reaction of the crystals is
weakly alkaline; the taste is somewhat bitter and pungent. Solanine
is soluble in 8000 parts of boiling water, 4000 parts of ether, 500
parts of cold, and 125 of boiling alcohol. It dissolves well in hot
amyl alcohol, but is scarcely soluble in benzene. An aqueous
solution froths on shaking, but not to the degree possessed by
saponine solutions.
The amyl alcohol solution has the property of gelatinising when
cold. It does this if even so little as 1 part of solanine is
dissolved in 2000 of hot amyl alcohol. The jelly is so firm that the
vessel may be inverted without any loss. This peculiar property is
one of the most important tests for the presence of solanine. The
hot ethylic alcohol solution will, on cooling, also gelatinise, but
a stronger solution is required. From very dilute alcoholic
solutions (and especially with slow cooling) solanine may be
obtained in crystals. In dilute mineral acids solanine dissolves
freely, and forms salts, which for the most part have an acid
reaction and are soluble in alcohol and in water, but with
difficulty in ether. The compounds with the acids are not very
stable, and several of them are broken up on warming the solution,
solanine separating out from the aqueous solutions of the solanine
salts. The alkaloid may be precipitated by the fixed and volatile
alkalies, and by the alkaline earths. Solanine will stand boiling
with strongly alkaline solutions without decomposition; but dilute
acids, on warming, hydrolyse. By heating solanine in alcoholic
solution with ethyl iodide in closed tubes, and then treating the
liquid with ammonia, ethyl solanine in well-formed crystals can be
obtained. Solanine is precipitated by phosphomolybdic acid, but by
very few other substances. It gives, for example, no precipitate
with the following reagents:--Platinic chloride, gold chloride,
mercuric chloride, potassic bichromate, and picric acid. Tannin
precipitates it only after a time. Sodic phosphate gives a
crystalline precipitate of solanine phosphate, if added to a
solution of solanine sulphate. Both solanine and solanidine give
with nitric acid at first a colourless solution, which, on gentle
warming, passes into blue, then into light red, and lastly becomes
weakly yellow. Solanine, dissolved in strong sulphuric acid, to
which a little Fröhde’s reagent is added, at first colours the fluid
light brown; after standing some time the edges of the drop becomes
reddish-yellow, and finally the whole a beautiful cherry-red, which
gradually passes into dark violet when violet-coloured flocks
separate.
§ 463. =Solanidine.=--Solanidine has stronger basic properties than
solanine. Its formula is C₄₀H₆₁NO₂. It is obtained from an alcoholic
solution in amorphous masses interspersed with needles; m.p. 191°.
It dissolves readily in hot alcohol, with difficulty in ether. With
hydrochloric acid it forms a hydrochloride--3(C₄₀H₆₁NO₂HCl)HCl + H₂O
or 1½H₂O. This hydrochloride is a slightly yellow powder, only
sparingly soluble in water, and carbonising without melting when
heated to 287°. Solanidine also forms a sulphate,
3(C₄₀H₆₁NO₂H₂SO₄)H₂SO₄ + 8H₂O; this salt is in the form of scaly
plates, melting at 247°; it dissolves readily in water.
The sugar obtained from the hydrolysis of solanidine is a yellow
amorphous mass dissolving readily in water and wood spirit, and has
a specific rotatory power of [α]_{D} = + 28·623. With
Phenylhydrazine hydrochloride and sodium acetate in aqueous solution
it forms a glucosazone, melting at 199°. It is probably a mixture of
sugars.
Solaneine is the name that has been given to the amorphous substance
accompanying solanine; on hydrolysis it yields solanidine and the
same sugar as solanine. Its formula is C₅₂H₈₂NO₁₃ with 4H₂O.
§ 464. =Poisoning from Solanine.=--Poisoning from solanine has been,
in all recorded cases, induced, not by the pure alkaloid (which is
scarcely met with out of the laboratory of the scientific chemist),
but by the berries of the different species of _Solanum_, and has
for the most part been confined to children. The symptoms in about
twenty cases,[517] which may be found detailed in the medical
literature of this century, have varied so greatly that the most
opposite phenomena have been witnessed as effects of poisoning by
the same substance. The most constant phenomena are a quick pulse,
laboured respiration, great restlessness, and hyperæsthesia of the
skin. Albumen in the urine is common. Nervous symptoms, such as
convulsions, aphasia, delirium, and even catalepsy, have been
witnessed. In some cases there have been the symptoms of an irritant
poison--diarrhœa, vomiting, and pain in the bowels: in many cases
dilatation of the pupil has been observed.
[517] See “Death of Three Children by _S. nigrum_”; Hirtz., _Gaz. Med.
de Strasbourg_, 1842; Maury, _Gaz. des Hôp._, 1864; J. B. Montane,
_Chim. Med._, 1862; Magne, _Gaz. des Hôp._, 1869; Manners, _Edin. Med.
Journ._, 1867. Cases of poisoning by bitter-sweet berries are recorded
in _Lancet_, 1856; C. Bourdin, _Gaz des Hôpitaux_, 1864; Bourneville,
the berries of _S. tuberosum_, _Brit. Med. Journ._, 1859.