DIVISION I.--POISONS SECRETED BY LIVING ANIMALS.
I.--Poisonous Amphibia.
§ 623. The glands of the skin of certain amphibia possess a secretion
that is poisonous; the animal is unable to empty the poison glands by
any voluntary act, but the secretion can readily be obtained by
pressure. Zalesky found the juice in the skin glands of the _Salamandra
maculosa_, milky, alkaline in reaction, and bitter in taste. He isolated
from it an organic base, which he named _Salamandrine_ (C₃₄H₆₀N₂O₅), it
is soluble in water and in alcohol, and forms salts. Salamandrine is a
strong poison; injected subcutaneously into rabbits it causes shivering,
epileptiform convulsions, and salivation; then tetanus, followed by
oppressed respiration, dilated pupils, and anæsthesia. Death occurs
after a kind of paralytic state. When given to dogs, it causes vomiting.
In frogs, tetanus occurs first and then paralysis--the result of all the
experiments being that salamandrine acts on the brain and spinal cord,
leaving the heart and muscular substance unaffected. A similar secretion
obtained from the water salamander (_Triton cristatus_), causes,
according to Vulpian, the death of dogs in from three to eighteen hours;
the symptoms being progressive weakness, slowing of the respiration, and
depression of the heart’s action.
§ 624. The secretion of the skin of the common toad contains
methylcarbylaminic acid, carbylamine, and, according to Fornara, an
alkaloid which is soluble in alcohol, and to which the name of
_phrynine_ has been applied; its action is toxic on all animals
experimented upon, save toads. Administered subcutaneously to frogs, it
has a digitalis-like action, causing rapid paralysis of the heart, and
the breathing soon after ceases; the muscles become early rigid.
II.--The Poison of the Scorpion.
§ 625. There are several species of scorpions. The small European
variety (_Scorpio europæus_) is found in Italy, the south of France, and
the Tyrol; the African scorpion (_Bothus afer_, L.), which attains the
length of 16 cm., is found in Africa and the East Indies; _Androctonus
bicolor_ in Egypt; and the _Androctonus occitanus_ in Spain, Italy,
Greece, and North Africa.
In the last joint of the tail the scorpion is provided with a poisonous
apparatus, consisting of two oval glands, the canal of which leads into
a round bladder, and this last is connected with a sting. When the sting
is inserted, the bladder contracts, and expels the poison through the
hollow sting into the wound. The smaller kinds of scorpion sting with as
little general effect as a hornet, but the large scorpion of Africa is
capable of producing death. There is first irritation about the wound,
and an erysipelatous inflammation, which may lead to gangrene. Vomiting
and diarrhœa then set in, with general weakness and a fever, which may
last from one to one and a half days; in the more serious cases there
are fainting, delirium, coma, convulsions, and death. According to G.
Sanarelli[632] the blood corpuscles of birds, fishes, frogs, and
salamanders are dissolved by the poison; only the nucleus remaining
intact; the blood corpuscles of warm-blooded animals are not affected.
[632] G. Sanarelli, _Bollet. della Soc. della sez. dei cult. delle
Scienze med._, v., 1888, 202.
Valentin made some experiments on frogs with the _Androctonus
occitanus_. He found that soon after the sting the animal remains quiet,
but on irritation it moves, and is thrown into a transitory convulsion;
to this follow twitchings of single muscular bundles. The frog is
progressively paralysed, and the reflex irritability is gradually
extinguished from behind forwards; at first the muscles may be excited
by electrical stimuli to the nerves, but later they are only capable of
contraction by direct stimuli.
III.--Poisonous Fish.
§ 626. A large number of fish possess poisonous properties; in some
cases the poison is local; in others the poison is in all parts of the
body.
Many fish are provided with poison glands in connection with the fins or
special weapons, and such are used for purposes of defence; for example,
_Synanceia brachio_ is provided with a back fin consisting of 13 spines,
each of which has two poison reservoirs; the reservoirs are connected
with 10 to 12 tubular glands which secrete the poison, a clear feebly
acid bluish fluid, exciting in a concentrated condition, local gangrene;
in a diluted one, paralysis of the nervous centres.
Another kind of localisation is the localisation in certain of the
internal organs. Remy states, that there are twelve varieties of
_Tetrodon_ in Japanese waters, all of which are poisonous. M. Minra and
K. Takesaki[633] find that the poison of the _Tetrodon_ is confined to
the sexual organs of the female, and at the time of activity of these
glands, the poisonous properties are most intense; but, even in winter,
when the glands are atrophied, Remy found the glands were so poisonous
that he could prepare from them a fluid, which, administered
subcutaneously, killed dogs within two hours. The symptoms in the dog
are restlessness, salivation, vomiting of slimy masses, dilatation of
the pupil, paralysis and great dyspnœa. Death occurs by the lung. After
death the appearances are similar to those from asphyxia; in addition to
which there are small ecchymoses in the stomach and intestines; the
salivary glands and pancreas are also injected. The symptoms observed in
man are similar, there is headache, dilated pupils, vomiting, sometimes
hæmatamesis, convulsions, paralysis, dyspnœa and death.
[633] Virchow’s _Archiv_, 1890, Bd. 122.
Some fishes are poisonous on account of the food they live upon; the
_Meletta venenosa_ is only poisonous when it feeds upon a certain green
monad; _Clupea thrissa_, _C. venenosa_ and certain species of _Scarus_,
neither possess poison glands nor poisonous ovaries; but also derive
their poisonous properties from their food. In the West Indies it is
well-known that fish caught off certain coral banks are unwholesome,
while the same species caught elsewhere may be eaten with safety.
A good many shell-fish, especially mussels, occasionally cause intense
poisonous symptoms; those usually noticed are high fever, nettle rash,
dilated pupils, and diarrhœa. It may be that in these cases a ptomaine,
the product of bacterial action, has been ingested. To the agency of
bacteria has been ascribed illness produced in Russia by a good many
fish of the sturgeon species. The symptoms are those of cerebro-spinal
paralysis. The “Icthyismus gastricus” of Germany may belong to the same
type. Prochorow[634] has described illness from ingestion of _Petromyzon
fluviatilis_ in Russia. Whether the fish was eaten raw or cooked, the
effect was the same, producing a violent diarrhœa, dysenteric in
character. Even the broth in which the fish had been boiled produced
symptoms. Fresh blood of the eel is stated to be intensely poisonous;
this property is apparently due to a toxalbumin; Pennavaria[635] relates
the case of a man who took, in 200 c.c. of wine, 0·64 kilo. of fresh eel
blood and suffered from diarrhœa with symptoms of collapse.
[634] _Pharmac. Ztg._, 1885.
[635] _Il Farmacista Italiano_, xii., 1888.
In the _Linnean Transactions_ for November, 1860, is recorded a fatal
accident, which took place on board the Dutch ship “Postillion” at
Simon’s Bay, Cape of Good Hope. The boatswain and purser’s steward
partook of the liver of the _toad_ or _ball-bladder_ (_Diodon_); within
twenty minutes the steward died; in ten minutes the boatswain was
violently ill; the face flushed, the eyes glistening, and the pupils
contracted; there was cyanosis of the face, the pulse was weak and
intermittent, and swallowing was difficult, the breathing became
embarrassed, and the body generally paralysed. Death took place in
seventeen minutes. The liver of one fish only is said to have been
eaten. This might weigh 4 drachms. If the account given is literally
correct, the intensity of the poison equals that of any known substance.
The poisonous nature of the goby has also led to several accidents, and
we possess a few experiments made by Dr. Collas,[636] who fed chickens
with different parts of the fish, and proved that all parts were alike
poisonous. The effects were slow in developing; they commenced in about
an hour or an hour and a half, and were well developed in five hours,
mainly consisting of progressive muscular weakness and prostration.
Death occurred without convulsions.
[636] _Soc. Sci. Rev._, July 19, 1862; _Brit. and For. Med. Chir. Rev._,
Oct. 1862, p. 536.
IV.--Poisonous Spiders and Other Insects.
§ 627. It is probable that all spiders are poisonous; the only species,
however, of which we have any definite information relative to their
poisonous properties, are _Lycosa tarantula_ and the _Latrodectus
malmignatus_, to which may be added the New Zealand _katipo_. These
spiders possess a poisonous gland connected with their masticatory
apparatus, which secretes a clear, oily, bitter acid-reacting fluid; the
acidity seems due to formic acid.
Zangrilli has observed several cases of tarantula bite; soon after the
occurrence the part bitten is anæsthetic, after a few hours there are
convulsive shiverings of the legs, cramps of the muscles, inability to
stand, spasm of the pharyngeal muscles, quickening of the pulse, and a
three days’ fever, with vomiting of yellow, bilious matter; recovery
follows after copious perspiration. In one case there was tetanus, and
death on the fourth day. The extraordinary effects attributed to the
bite of the tarantula, called _tarantism_ in the Middle Ages, are well
detailed by Hecker;[637] this excitement was partly hysterical and
partly delirious, and has not been observed in modern times.
[637] “The Epidemics of the Middle Ages,” by J. F. C. Hecker, translated
by B. G. Babington, M.D., F.R.S. (_The Dancing Mania_, chap, ii., &c.)
Dax has described the effects of the bite of the _L. malmignatus_; it
occasioned headache, muscular weakness, pain in the back, cramps, and
dyspnœa; the symptoms disappeared after several days.
§ 628. The _katipo_ is a small poisonous spider confined to New Zealand.
Mr. W. H. Wright has recorded the case of a person who, in 1865, was
bitten by this spider on the shoulder. The part rapidly became swollen,
and looked like a large nettle-rash wheal; in an hour the patient could
hardly walk, the respiration and circulation were both affected, and
there was great muscular prostration; but he recovered in a few hours.
In other cases, if the accounts given are to be relied upon, the bite of
the spider has produced a chronic illness, accompanied by wasting of the
body, followed by death after periods varying from six weeks to three
months.[638]
[638] _Transac. of the New Zealand Inst._, vol. ii., 1869; _Brit. and
For. Med. Chir. Review_, July 1871, p. 230.
§ 629. =Ants.=--The various species of ants possess at the tail special
glands which secrete _formic acid_. Certain exotic species of ants are
provided with a sting, but the common ant of this country has no special
piercing apparatus. The insect bites, and then squirts the irritating
secretion into the wound, causing local symptoms of swelling and
inflammation.
§ 630. =Wasps, &c.=--Wasps, bees, and hornets all possess a poison-bag
and sting. The fluid secreted is as clear as water, and of an acid
reaction; it certainly contains formic acid, with some other poisonous
constituent. An erysipelatous inflammation generally arises round the
sting, and in those cases in which persons have been attacked by a swarm
of bees, signs of general poisoning, such as vomiting, fainting,
delirium, and stupor, have been noticed. Death has occasionally
resulted.
§ 631. =Cantharides.=--Commercial cantharides is either the dried
entire, or the dried and powdered blister-beetle, or Spanish fly
(_Cantharis vesicatoria_). The most common appearance is that of a
greyish-brown powder, containing shining green particles, from which
cantharidin is readily extracted by exhausting with chloroform, driving
off the chloroform by distillation or evaporation, and subsequently
treating the extract with bisulphide of carbon, which dissolves the
fatty matters only. Finally, the cantharidin may be recrystallised from
chloroform, the yield being ·380 to ·570 per cent. Ferrer found in the
wings and their cases, ·082 per cent.; in the head and antennæ, ·088; in
the legs, ·091; in the thorax and abdomen, ·240; in the whole insect,
·278 per cent. Wolff found in the _Lytta aspera_, ·815 per cent.; Ferrer
in _Mylabris cichorei_, ·1 per cent.; in _M. punctum_, ·193; and in _M.
pustulata_, ·33 per cent. of _cantharidin_.
§ 632. =Cantharidin= (C₁₀H₁₂O₄) has two crystalline forms--(1)
Right-angled four-sided columns with four surfaces, each surface being
beset with needles; and (2) flat tables. It is the anhydride of a ketone
acid (cantharidic acid), C₈H₁₃O₂-CO-COOH. It is soluble in alkaline
liquids, and can be recovered from them by acidifying and shaking up
with _ether_, _chloroform_, or _benzene_; it is almost completely
insoluble in water. 100 parts of alcohol (99 per cent.) dissolve at 18°
0·125 part; 100 of bisulphide of carbon, at the same temperature, 0·06
part; ether, ·11 part; chloroform, 1·2 part; and benzene, ·2 part.
Cantharidin can be completely sublimed, if placed in the subliming cell
(described at p. 258), floating on mercury; a scanty sublimate of
crystals may be obtained at so low a temperature as 82·5°; at 85°, and
above, the sublimation is rapid. If the cantharidin is suddenly heated,
it melts; but this is not the case if the temperature is raised
gradually. The tube melting-point is as high as 218°. Potassic chromate
with sulphuric acid decomposes cantharidin with the production of the
green oxide of chromium. An alkaline solution of permanganate, iodic
acid, and sodium amalgam, are all without influence on an alcoholic
solution of cantharidin. With bases, cantharidin forms crystallisable
salts, and, speaking generally, if the base is soluble in water, the
“_cantharidate_” is also soluble; the lime and magnesic salts dissolve
readily. From the soda or potash salt, mineral acid will precipitate
crystals of cantharidin; on heating with pentasulphide of phosphorus,
o-xylol is produced.
§ 633. =Pharmaceutical Preparations of Cantharides.=--The P.B.
preparations of cantharides are--_Acetum cantharides_, or vinegar of
cantharides, containing about ·04 per cent. of cantharidin.
_Tincture of cantharides_, containing about ·005 per cent. of
cantharidin.
A solution of cantharides for blistering purposes, _Liquor
epispasticus_, a strong solution of the active principle in ether and
acetic acid, containing about ·16 per cent. of cantharidin.
There are also--An _ointment_; a blistering paper, _Charta epispastica_;
a blistering plaster, _Emplastrum cantharides_; and a warm plaster,
_Emplastrum calefaciens_.
§ 634. =Fatal Dose.=--It is difficult to state the fatal dose of
cantharidin, the unassayed powder or tincture having mostly been taken.
A young woman died from 1·62 grm. (25 grains) of the powder, which is
perhaps equivalent to 6·4 mgrms. (1 grain) of cantharidin, whilst the
smallest dose of the tincture known to have been fatal is (according to
Taylor) an ounce. This would be generally equivalent to 15 mgrms. (·24
grain). Hence the fatal dose of cantharidin may be approximately stated
as from 6 mgrms. upwards. But, on the other hand, recovery has taken
place from very large doses.
§ 635. =Effects on Animals.=--Certain animals do not appear susceptible
to the action of cantharidin. For example, hedgehogs and swallows are
said to be able to take it with impunity. Radecki[639] found that
cantharidin might even be injected into the blood of fowls without any
injury, and frogs also seem to enjoy the same impunity; while dogs,
cats, and other animals are sensitive to the poison. Galippe ascertained
that after the injection of 5 mgrms. into the veins of a dog, there was
exaltation of the sexual desire; the pupils quickly dilated, the dog
sought a dark place, and became sleepy. Animals when poisoned die in
asphyxia from paralysis of the respiratory centre. Schachowa[640] made
some observations on the effect of cantharides on the renal excretion of
a dog fed daily with 1 grm. in powder. On the third day, pus corpuscles
were noticed; on the fifth, bacteria; on the thirteenth, the urine
contained a large quantity of fatty matters, and several casts; and on
the seventeenth, red shrivelled blood corpuscles were observed.
[639] _Die Cantharidin Vergift._, Diss., Dorpat, 1806.
[640] _Unters. über die Nieren_, Diss., Bern, 1877; Cornil, _Gaz. Méd._,
1880.
=Effects on Man.=--Heinrich[641] made the following experiments upon
himself:--Thirty living blister-beetles were killed, and digested,
without drying, in 35 grms. of alcohol for fourteen days, of this
tincture ten drops were taken. There ensued immediately a feeling of
warmth in the mouth and stomach, salivation, the pulse was more frequent
than in health, there was a pleasant feeling of warmth about the body,
and some sexual excitement lasting three hours. In half an hour there
was abdominal pain, diarrhœa, and tenesmus, and frequent painful
micturition. These symptoms subsided in a few hours, but there was a
want of appetite, and pain about the kidneys lasting until the following
day. In the second experiment, on taking 1 cgrm. of cantharidin, there
were very serious symptoms of poisoning. Blisters formed on the tongue,
and there was salivation, with great difficulty in swallowing, and a
general feeling of illness. Seven hours after taking the poison, there
were frequent micturitions of bloody urine, diarrhœa, and vomiting.
Twenty hours after the ingestion the face was red, the skin hot, the
pulse twenty beats beyond the normal pulsation, the tongue was denuded
to two-thirds of its extent of its epithelium, and the lips and mucous
membrane were red and swollen; there was great pain in the stomach,
intestines, and in the neighbourhood of the kidneys, continuous desire
to micturate, burning of the urethra, and swelling of the glands. There
was no sexual excitement whatever; the urine was ammoniacal, and
contained blood and pus; the symptoms gradually subsided, but recovery
was not complete for fourteen days.
[641] Schroff, _Zeitschrift d. Ges. d. Aerzte in Wien_, 13, 56.
§ 636. The foregoing is a fair picture of what may be expected in
cantharides poisoning. It is remarkable that the popular idea as to the
influence of cantharidin in exciting the sexual passion, holds good only
as to the entire cantharides, and not with cantharidin. It is very
possible that cantharidin is not the only poisonous principle in the
insect. The symptoms in other cases, fatal or not, have been as
follows:--Immediate burning in the mouth and throat, extending to the
stomach and alimentary canal, and increasing in intensity until there is
considerable pain. Then follow salivation, difficulty in swallowing, and
vomiting, and generally diarrhœa, pain in the kidneys, irritation of the
bladder, priapism, and strangury, are all present. The pulse is
accelerated, the breathing disturbed, there are pains in the head, and
often mydriasis, giddiness, insensibility, delirium, and convulsions;
trismus has been noticed. The desire to micturate frequently is urgent,
the urine is generally bloody, and contains pus. Pregnant women have
been known to abort. In a few of the cases in which a different course
has been run, the nervous symptoms have predominated over those of
gastro-intestinal irritation, and the patient has sunk in a kind of
collapse. In a case of chronic poisoning by cantharides, extending over
three months, and recorded by Tarchioni Bonfanti,[642] after the first
dose appeared tetanic convulsions, which subsided in twenty-four hours,
there was later cystitis, and from time to time the tetanic convulsions
returned; gastro-enteritis followed with frequent vomiting, when,
cantharides being found in the matters ejected, the otherwise obscure
nature of the illness was shown.
[642] _Gaz. Med. Ital. Lomb._, 1863.
In a case recorded by Sedgwick,[643] following the gastro-enteric
symptoms, there were epileptic convulsions; in this instance also was
noticed an unpleasant smell, recalling the notion formerly held that
cantharides imparted a peculiar odour to the breath and urine. In a case
of chronic poisoning related by Tardieu, six students, during several
months, used what they thought was pepper with their food, but the
substance proved to be really powdered cantharides. The quantity taken
each day was probably small, but they suffered from pain about the
loins, and also irritation of the bladder. There was no sexual
excitement.
[643] _Med. Times_, 1864.
§ 637. =Post-mortem Appearances.=--In a French criminal case, in which a
man poisoned his step-brother by giving cantharides in soup, the
pathological signs of inflammation of the gastro-intestinal tract were
specially evident, the mouth was swollen, the tonsils ulcerated, the
gullet, stomach, and intestines were inflamed, and the mucous membrane
of the intestines covered with purulent matter. In another case there
was an actual perforation 3 inches from the pylorus. The inflammatory
appearances, however, are not always so severe, being confined to
swelling and inflammation without ulceration. In all cases there has
been noted inflammation of the kidneys and urinary passages, and this is
seen even when cantharidin is administered to animals by subcutaneous
injection. In the urine will be found blood and fatty epithelial casts,
as well as pus. The contents of the stomach or the intestines will
probably contain some remnants of powdered cantharides, if the powder
itself has been taken.
§ 638. =Tests for Cantharidin, and its Detection in the Tissues,
&c.=--The tests for cantharidin are--(1.) Its form, (2.) its action in
the subliming cell, and (3.) its power of raising a blister.
The most convenient method of testing its vesicating properties, is to
allow a chloroformic solution of the substance supposed to be
cantharidin to evaporate to dryness, to add to this a drop of olive oil
(or almond oil), and to take a drop up on the smallest possible quantity
of cotton wool, and apply the wool to the inside of the arm, covering it
with good oilskin, and strapping the whole on by the aid of
sticking-plaster. In about an hour or more the effect is examined. The
thin skin of the lips is far more easily blistered than that of the arm,
but the application there is inconvenient.
Dragendorff has ascertained that cantharidin is not present in the
contents of a blister raised by a cantharides plaster, although it has
been found in the urine of a person treated by one; and Pettenkofer has
also discovered cantharidin in the blood of a boy to whose spine a
blister had been applied.
The great insolubility of cantharidin in water has led to various
hypotheses as to its absorption into the system. It is tolerably easily
dissolved by potash, soda, and ammonia solutions, and is also taken up
in small proportion by sulphuric, phosphoric, and lactic acids. The
resulting compounds quickly diffuse themselves through animal membranes.
Even the salts with lime, magnesia, alumina, and the heavy metals, are
not quite insoluble. A solution of salt with cantharidin, put in a
dialysing apparatus, separates in twenty-four hours enough cantharidin
to raise a blister.
Cantharidin has actually been discovered in the heart, brain, muscles,
contents of the stomach, intestines, and fæces (as well as in the blood
and urine) of animals poisoned by the substance. A urine containing
cantharidin is alkaline and albuminous. Cantharidin, although readily
decomposed by chemical agents, is so permanent in the body that it has
been detected in the corpse of a cat eighty-four days after death.
In any forensic case, the defence will not improbably be set up that
some animal (_e.g._, a fowl poisoned by cantharides) has been eaten and
caused the toxic symptoms, for cantharides is an interesting example of
a substance which, as before stated, for certain animals (such as
rabbits, dogs, cats, and ducks), is a strong poison, whilst in others
(_e.g._, hedgehogs, fowls, turkeys, and frogs), although absorbed and
excreted, it appears inert. Experiment has shown that a cat may be
readily poisoned by a fowl saturated with cantharides; and in Algeria
the military surgeons meet with cystitis among the soldiers, caused by
eating frogs in the months of May and June, the frogs living in these
months almost exclusively on a species of cantharides.
Dragendorff recommends the following process:--The finely-pulped
substance is boiled in a porcelain dish with potash-lye (1 part of
potash and 12 to 18 of water) until the fluid is of a uniform
consistence. The fluid, after cooling, is (if necessary) diluted with an
equal bulk of water, for it must not be too thick; then shaken with
chloroform in order to remove impurities; and after separation of the
chloroform, strongly acidified with sulphuric acid, and mixed with about
four times its volume of alcohol of 90 to 95 per cent. The mixture is
kept for some time at a boiling temperature, filtered hot, and the
alcohol distilled from the filtrate. The watery fluid is now again
treated with chloroform, as above described. The chloroform extract is
washed with water, the residue taken up on some hot almond oil, and its
blistering properties investigated. The mass, heated with potash in the
above way, can also be submitted to dialysis, the diffusate
supersaturated with sulphuric acid, and shaken up with chloroform.
In order to test further for cantharidin, it can be dissolved in the
least possible potash or soda-lye. The solution, on evaporation in the
water-bath, leaves crystals of a salt not easily soluble in alcohol, and
the watery solution of which gives with chloride of calcium and baryta a
white precipitate; with sulphate of copper and sulphate of protoxide of
nickel, a green; with cobaltous sulphate, a red; with sugar of lead,
mercury chloride and argentic nitrate, a white crystalline precipitate.
With palladium chloride there occurs a yellow, hair-like, crystalline
precipitate; later crystals, which are isomorphous with the nickel and
copper salts.
If the tincture of cantharides has been used in considerable quantity,
the urine may be examined; in such a case there will collect on the
surface drops of a green oil, which may be extracted by petroleum ether;
this oil is not blister-raising. Cantharides in powder may, of course,
be detected by its appearance.
To the question whether the method proposed would extract any other
blister-producing substance, the answer is negative, since ethereal oil
of mustard would be decomposed, and the active constituents of the
_Euphorbias_ do not withstand the treatment with KHO. Oils of anemone
and anemonin are dissolved by KHO, and again separated out of their
solutions, but their blistering property is destroyed. They are
volatile, and found in anemone and some of the _Ranunculaceæ_. In the
_Aqua pulsatilla_ there is an oil of anemone, which may be obtained by
shaking with ether; but this oil is not permanent, and if the _Aqua
pulsatilla_ stand for a little time, it splits up into anemonic acid and
anemonin, and then cannot be reobtained. A blistering substance,
obtained from the _Anacardia orientalia_ and the fruit of the
_Anacardium occidentale_ and _Semecarpus anacardium_, is not quite
destroyed by a short action with potash, but is by one of long duration;
this substance, however, cannot be confused with cantharidin, for it is
oily, yellow, easily soluble in alcohol and ether, and differs in other
respects.
V.--Snake Poison.
§ 639. The poisonous snakes belong chiefly to two classes, the
_Proteroglypha_ and the _Solenoglypha_.
Weir Mitchell and Ed. T. Reichert[644] have made some important
experiments on snake poison, using the venom of some 200 snakes. Most of
the snakes were rattlesnakes, a few were cobras and other species. They
came to the conclusion that the active constituents are contained in the
fluid part alone, the solid particles suspended in the fluid having no
action. The poison they considered to consist of two toxalbumins, one a
globulin, acting more particularly on the blood, the other, a peptone
(albumose?), acting more particularly on the tissues. Differences in
snake venom depend on the relative proportions of these two substances.
The peptone, which acts more especially locally on the tissues,
determines an inflammatory action, with much swelling and multiple
extravasation of blood, which may proceed to a moist gangrene. The
globulin has a paralysing influence on the heart, the vasomotor centres,
the peripheral ends of the splanchnic nerves, as well as on the
respiratory centres of both warm and cold-blooded animals.
Feoktisow’s[645] researches show that although the heart continues to
beat after the respiration has ceased for a few minutes, it has no
force. The blood pressure sinks immediately after the injection. Whether
the globulin is injected subcutaneously or direct into the veins, there
is commonly considerable extravasation of blood in the chest and
abdomen; the intestine is often filled with blood as well as the
pericardium; and the urine is bloody. The poison of _Vipera ammodytes_
in watery solution may be boiled for six minutes, and yet is as active
as before. According to Lewin, snake poison generally can be heated to
125° and yet preserve its poisonous properties. These last observations
are not in accordance with the belief of some that the active principle
of snake venom is a ferment, or, indeed, in harmony with the idea that
it is a globulin or toxalbumin; for such bodies have not, so far as we
know, the stability to withstand so high a degree of heat.
[644] _Smithsonian Contributions to Knowledge_, Washington, 1886.
[645] _Exp. Unters. über Schlangengift. Inaug. Diss._, Dorpat, 1888.
§ 640. =The Poison of the Cobra.=--The poison excreted from the salivary
glands of the cobra di capello is the most deadly animal fluid known.
When first ejected, it is an amber-coloured, rather syrupy, frothy
liquid, of specific gravity 1·046, and of feeble acid reaction; it dries
rapidly on exposure to air to a yellow film, which readily breaks up
into brilliant yellow granules, closely imitating crystals. The yellow
powder is very acrid and pungent to the nostrils, and excites a painful
(though transitory) inflammation, if applied to the mucous membrane of
the eye; the taste is bitter, and it raises little blisters on the
tongue. It is perfectly stable, and preserves its activity for an
indefinite time. The dried poison as described is perfectly soluble in
water, and if the water is added in proper proportions, the original
fluid is without doubt reproduced, the solution usually depositing a
sediment of epithelial _débris_, and often containing little white
threads.
The poison has been examined by several chemists, but until of late
years with a negative result. The writer was the first to isolate, in
1876, a crystalline principle, which appears to be the sole acting
ingredient; the yellow granules were dissolved in water, the albumen
which the venom so copiously contains coagulated by alcohol, and
separated by filtration; the alcohol was then driven off at a gentle
heat, the liquid concentrated to a small bulk, and precipitated with
basic acetate of lead. The precipitate was separated, washed, and
decomposed in the usual way by SH₂, and on removing the lead sulphide,
crystals having toxic properties were obtained.
Pedler,[646] precipitating the albumen by alcohol, and then to the
alcoholic solution adding platinic chloride, obtained a semi-crystalline
precipitate, which from an imperfect combustion he thinks may have
something like the composition PtCl₄(C₁₇H₂₅N₄O₇HCl)₂. I have examined
the platinum compound, and made several combustions of different
fractions, but was unable to obtain the compound in a sufficient state
of purity to deduce a formula. My analysis agreed with those of Pedler
for nitrogen--viz., 9·93 per cent. (Pedler, 9·69); hydrogen 4·17
(Pedler, 4·28); but were higher for carbon, 41·8 per cent. (Pedler,
33·42 per cent.); one fraction gave 7·3 per cent. of platinum, another
double that amount. Material was insufficient to thoroughly investigate
the compound, but it was evident that several double salts were formed.
The blood of the cobra is also poisonous. A. Calmette[647] has found
that 2 c.c. of fresh cobra blood, injected into the peritoneum of a
rabbit weighing 1·5 kilo., causes death in six hours; the same dose of
the defibrinated blood injected into the veins is fatal in three
minutes.
[646] _Proc. Roy. Soc._, vol. xxvii. p. 17.
[647] _Compt. Rend., Soc. de Biol._, 1894.
§ 641. =Fatal Dose.=--From my experiments on cats, rabbits, and birds,
it seems probable that the least fatal dose for cats and rabbits, lies
between ·7 and ·9 mgrm. per kilo., and for birds somewhere about ·7
mgrm. per kilo. of the dried poison; the venom contains about 60 per
cent. of albuminous matter, and about 10 per cent. of poisonous
substance; therefore, the lethal power is represented by something like
·07 to ·09 mgrm. per kilo., if the pure toxic principle free from
albumen and diluting impurities be considered.
§ 642. =Effects on Animals.=--Almost immediately local pain or signs of
uneasiness at the seat of injection are observed. There is then a
variable interval, seldom exceeding 20 minutes (and generally much
less), but in one of my experiments half an hour elapsed after the
injection of a fatal dose before any effect was evident. The symptoms
once produced, the course is rapid, and consists, first, of acceleration
of the respirations, and then a progressive slowing, soon followed by
convulsions. The convulsions are probably produced by the interference
with the respiration and the deficient oxidation of the blood, and are
therefore, the so-called “carbonic acid convulsions.” There is paresis
or paralysis of the limbs. Death seems to occur from asphyxia, and the
heart beats for one or more minutes after the respirations have ceased.
If the dose is so small as not to produce death, no after-effects have
been observed; recovery is complete.
Sir J. Fayrer, and Dr. Lauder Brunton consider that the terminations of
the motor nerves suffer; on the other hand, Dr. Wall would explain the
phenomena by referring the action entirely to the central nervous
system, and concludes that the effects of the cobra poison consist in
the extinction of function extending from below upwards of the various
nerve centres constituting the cerebro-spinal system. In addition to
this, there is a special and rapid action on the respiratory and allied
nuclei, and this it is that causes death.
§ 643. =Effects on Man.=--By far the best account hitherto published of
the effects of the cobra poison is a paper by Dr. Wall,[648] in which he
points out the very close similarity between the symptoms produced and
those of glosso-pharyngeal paralysis. This is well shown in the
following typical case:--A coolie was bitten on the shoulder about
twelve at midnight by a cobra; he immediately felt burning pain at the
spot bitten, which increased. In fifteen minutes afterwards he began, he
said, to feel intoxicated, but he seemed rational, and answered
questions intelligently. The pupils were natural, and the pulse normal;
the respirations were also not accelerated. He next began to lose power
over his legs, and staggered. In thirty minutes after the bite his lower
jaw began to fall, and frothy viscid mucous saliva ran from his mouth;
he spoke indistinctly, like a man under the influence of liquor, and the
paralysis of the legs increased. Forty minutes after the bite, he began
to moan and shake his head from side to side, and the pulse and
respirations were somewhat accelerated; but he was still able to answer
questions, and seemed conscious. There was no paralysis of the arms. The
breathing became slower and slower, and at length ceased one hour and
ten minutes after the bite, the heart beating for about one minute after
the respiration had stopped.
[648] “On the Difference of the Physiological Effects Produced by the
Poison of Indian Venomous Snakes,” by A. T. Wall, M.D., _Proc. Roy.
Soc._, 1881, vol. xxxii. p. 333.
There is often very little sign of external injury, merely a scratch or
puncture being apparent, but the areolar tissue lying beneath is of a
purple colour, and infiltrated with a large quantity of coagulable,
purple, blood-like fluid. In addition, the whole of the neighbouring
vessels are intensely injected, the injection gradually diminishing as
the site of the poisoned part is receded from, so that a bright scarlet
ring surrounds a purple area, and this in its turn fades into the normal
colour of the neighbouring tissues. At the margin is also a purple
blood-like fluid, replaced by a pinkish serum, which may often be traced
up in the tissues surrounding the vessels that convey the poison to the
system, and may extend a considerable distance. These appearances are to
be accounted for in great part by the irritant properties of the cobra
venom. The local hyperæmia and the local pain are the first symptoms. In
man there follows an interval (which may be so short as a few minutes,
or so long as four hours) before any fresh symptoms appear; the average
duration of the interval is, according to Dr. Wall, about an hour. When
once the symptoms are developed, then the course is rapid, and, as in
the case quoted, a feeling like that of intoxication is first produced,
and then loss of power over the legs. This is followed by a loss of
power over the speech, over swallowing, and the movement of the lips;
the tongue becomes motionless, and hangs out of the mouth; the saliva is
secreted in large quantities, and runs down the face, the patient being
equally unable to swallow it or to eject it, and the glosso-pharyngeal
paralysis is complete.
§ 644. =Antidotes and Treatment.=--Professor Halford some years ago
proposed ammonia, and M. Lacerda in recent times has declared potassic
permanganate an antidote to the cobra poison. The ammonia theory has
been long disproved, and before Lacerda had made his experiments I had
published the chemical aspect of some researches,[649] which showed that
mixing the cobra venom with an alkaline solution of potassic
permanganate destroyed its poisonous properties. Other experiments were
also made in every conceivable way with potassic permanganate, injecting
it separately, yet simultaneously, into different parts of the same
animal’s body, but so long as it does not come into actual contact with
the poison it has no antidotal power whatever over the living subject.
Other observers, previous to the researches mentioned and since, all
agree that permanganate is no true antidote.[650] It only acts when it
comes directly into contact with the venom, but when the venom is once
absorbed into the circulation potassic permanganate, whether acid,
alkaline, or neutral, is powerless. That it is of great use when applied
to a bite is unquestionable, for it neutralises or changes any of the
venom hanging about the wound, and which, if allowed to remain, might
yet be absorbed; but here it is obvious that the venom is, so to speak,
outside the body. A. Galmette (_Annales de l’Institut Pasteur_, 25th
March 1892) has found that gold chloride forms an insoluble compound
with the cobra poison, which is not poisonous, and that animal living
tissues impregnated with gold chloride will not absorb the poison. He
even advances some evidence tending to show that gold chloride may
overtake, as it were, the venom in the circulation, and thus act as a
true antidote. This is improbable, and, until confirmed, the general
treatment most likely to be successful is the immediate sucking of the
wound, followed by the application of an alkaline solution of
permanganate; and lastly, if the symptoms should nevertheless develop,
an attempt should be made to maintain the breathing by galvanism and
artificial respiration.[651]
[649] _Analyst_, Feb. 28, 1877.
[650] See Note on the effect of various substances in destroying the
activity of the cobra poison. By T. Lauder Brunton and Sir J. Fayrer,
_Proc. Roy. Soc._, vol. xxvii. p. 17.
[651] Some of my experiments on the cobra poison may be briefly
detailed, illustrating the general statement in the text:--
1. A quantity equal to 1 mgrm. of the dried venom was injected
subcutaneously into a chicken. The symptoms began in two minutes with
loss of power over both legs. In eight minutes the legs were perfectly
paralysed. There were convulsive movements of the head and wings,
slowing of the respiration, and death in ten minutes. The same quantity
of poison was treated with a little tannin, and the clear liquid which
separated from the precipitate injected into another chicken. The
respiration became affected in ten minutes; in eighteen minutes the bird
had become very quiet, and lay insensible; in twenty minutes it was
dead, the respiration ceasing before the heart.
2. In seven experiments with cobra poison, first rendered feebly
alkaline with an alkaline solution of potassic permanganate, no effect
followed. Three of the experiments were on chickens, four on rabbits.
3. A chicken was injected with 1 mgrm. of cobra poison in one leg, and
in the other simultaneously with a solution of potassic permanganate.
Death followed in sixteen minutes. Another chicken was treated in the
same way, but with injections of potassic permanganate solution every
few minutes. Death resulted in thirty-seven minutes. Four other similar
experiments were made--two with feebly alkaline permanganate, two with
permanganate made feebly acid with sulphuric acid--but death occurred
with the usual symptoms.
4. Cobra poison was mixed with a weak solution of iodine, and a quantity
equal to half a mgrm. was injected into a chicken. The symptoms began
directly, were fully developed in ten minutes, and death took place in
twenty-one minutes.
5. Equal volumes of cobra venom and aldehyde were mixed, and a quantity
equivalent to 1 mgrm. of the cobra poison injected. The symptoms were
immediate paralysis and insensibility, and the respiration rapidly fell.
Death occurred in four minutes without convulsions.
6. The cobra venom was mixed with a feebly alkaline solution of
pyrogallic acid, and injected subcutaneously into a chicken. In six
minutes the usual symptoms commenced, followed in thirteen minutes by
death.
7. One mgrm. was injected into a chicken. The respirations at the
commencement were 120; in twenty-two minutes they sank to 96, in
twenty-five minutes to 84, in twenty-seven minutes to 18, and then to
occasional gasps, with slight movement of the wings and toes. There was
death in thirty-two minutes after the injection.
8. A young rabbit was injected with ·5 mg. (equal to 1 mgrm. per kilo.)
of cobra poison. In two hours it was apparently moribund, with
occasional short gasps. Artificial respiration was now attempted. There
was considerable improvement, but it was intermitted during the night,
and the animal was found dead in the morning, having certainly lived six
hours.
9. A strong healthy kitten was injected with 1 mgrm. of cobra venom
(equal to 5 mgrms. per kilo.). In twenty minutes the symptoms were well
developed, and in an hour the animal was gasping--about twelve short
respirations per minute. Artificial respiration was kept up for two
hours, and the animal recovered, but there was great muscular weakness
lasting for more than twenty-four hours.
10. A brown rabbit, weighing about 2 kilos., was injected with 12 mgrms.
(6 per kilo.) of the cobra poison. The symptoms developed within ten
minutes; ammonia was injected, and also given by the nostril. The
heart’s action, which, previous to the administration of the ammonia,
had been beating feebly, became accelerated, but death followed within
the hour, the heart beating two minutes after the respiration had
ceased.
11. A brown rabbit, about 2 kilos. in weight, was injected with 1·5
mgrms. of cobra poison (·75 per kilo.). There were no symptoms for
nearly an hour, then sudden convulsions, and death.
12. Another rabbit of the same size was treated similarly, but
immediately after the injection made to breathe nitrous oxide; death
took place in thirty minutes. A rabbit, a little over 2 kilos. in
weight, was injected with 7 mgrms. of cobra venom per kilo., and then 10
mgrms. of monobromated camphor were administered. In fifteen minutes
there was general paralysis of the limbs, from which in a few minutes
the animal seemed to recover; thirty minutes after the injection there
were no very evident symptoms, but within forty minutes there was a
sudden accession of convulsions, and death. Experiments were also made
with chloroform, morphine, and many other substances, but none seemed to
exercise any true antidotal effect.
§ 645. =Detection of the Cobra Venom.=--In an experiment on a rabbit,
the animal was killed by the subcutaneous injection of 8 mgrms. per
kilo. of the cobra poison. Immediately after death, 2 c.c. of the blood
were injected into a small rabbit; in fifteen minutes there was slow
respiration with pains in the limbs; in thirty minutes this had, in a
great measure, passed off, and in a little time the animal was well. In
any case in which it is necessary to attempt to separate the cobra
venom, the most likely method of succeeding would be to make a cold
alcoholic extract, evaporate in a vacuum, take up the residue in a
little water, and test its effect on small animals.
§ 646. =Duboia Russellii.=--The _Duboia russellii_ or _Russell’s viper_
is one of the best known and most deadly of the Indian vipers. The
effects of the poison of this viper are altogether different from those
of the cobra. The action commences by violent general convulsions, which
are often at once fatal, or may be followed by rapid paralysis and
death; or these symptoms, again, may be recovered from, and death follow
at a later period. The convulsions do not depend on asphyxia, and with a
small dose may be absent. The paralysis is general, and may precede for
some time the extinction of the respiration, the pupils are widely
dilated, there are bloody discharges, and the urine is albuminous.
Should the victim survive the first effects, then blood-poisoning may
follow, and a dangerous illness result, often attended with copious
hæmorrhages. A striking example of this course is recorded in the
_Indian Med. Gaz._, June 1, 1872.
A Mahommedan, aged 40, was bitten on the finger by Russell’s viper; the
bitten part was soon after excised, and stimulants given. The hand and
arm became much swollen, and on the same day he passed blood by the
rectum, and also bloody urine. The next day he was sick, and still
passing blood from all the channels; in this state he remained eight
days, losing blood constantly, and died on the ninth day. Nothing
definite is known of the chemical composition of the poison; it is
probably qualitatively identical with “viperin.”
§ 647. =The Poison of the Common Viper.=--The common viper still abounds
in certain parts of Great Britain, as, for example, on Dartmoor. The
venom was analysed in a partial manner by Valentin. In 1843 Prince
Lucien Bonaparte separated a gummy varnish, inodorous, glittering, and
transparent, which he called _echidnin_ or _viperin_; it was a neutral
nitrogenous body without taste, it arrested the coagulation of the
blood, and, injected into animals, produced all the effects of the bite
of the viper. Phisalix and G. Bertrand have studied the symptoms
produced in small animals after injection. A guinea-pig, weighing 500
grms., was killed by 0·3 grm. of the dried venom dissolved in 5000 parts
of saline water; the symptoms were nausea, quickly passing into stupor.
The temperature of the body fell. The autopsy showed the left auricle
full of blood, the intestine, lungs, liver, and kidneys injected. The
blood of the viper is also poisonous, and produces the same symptoms as
the venom.[652] The same observers have shown (_Compt. rend._, cxviii.,
Jan. 1894) that the blood of the water-snake (_Tropidonotus natrix_) and
of the Thuringian adder (_Tropidonotus viperinus_) is poisonous,
producing the same symptoms as that of the viper.
[652] _Compt. rend. Soc. de Biol._, t. v. 997.
=The Venom of Naja Haje= (=Cleopatra’s Asp=).--It has been stated that
20,000 persons annually die in Ceylon from the bite of Cleopatra’s asp.
Graziani (_Rif. Med._, October 7, 1893) has undertaken a physiological
study of the venom, which has already received attention at the hands of
Calmette, Wall and Armstrong, Weir Mitchell, Reichardt, and others. The
venom, when dried, appears as transparent scales, easily soluble in
water, very slightly so in alcohol, ether, or chloroform; its aqueous
solution has an unpleasant odour, and is neutral to test paper.
Chemically it gives all the tests described by Weir Mitchell and others
as characteristic of the venom of _Naja tripudians_. The physiological
effects of this dried venom were tried on guinea-pigs, rabbits, and
frogs, to all of which it proved fatal in extremely minute doses. The
guinea-pig, a few seconds after injection, becomes paralysed in its hind
limbs, it foams at the mouth, and makes violent attempts at vomiting.
The eyes are half closed, but occasionally for short periods there is a
partial disappearance of the paralysis, and the animal makes feeble
attempts to support itself. Respiratory embarrassment is soon added to
the foregoing symptoms, and the animal lies perfectly prone, devoting
all its attention to breathing, which is rendered still more difficult
by the vomiting and frothy saliva which is secreted in abundance.
Finally death ensues from asphyxia. The _post-mortem_ examination
reveals the heart still feebly beating, the lungs pallid, and the blood
in the organs very dark. The liver and kidneys are hyperæmic, but the
brain and cord, with their coverings, are anæmic. In the rabbit the
course of the poisoning is practically identical with that described
above. Histologically, the following facts are made out in addition to
the foregoing. The red blood-corpuscles are in great measure broken
down, and there are also effusions into the muscular tissues. The
kidneys are very hyperæmic, and there is marked degeneration of the
epithelium lining the glomeruli and convoluted tubules. The glomerular
capsules are much distended, and numerous leucocytes are discernible
throughout the organ. The liver, also, is hyperæmic, and shows numerous
broken-down blood-corpuscles, and partial necrosis of many of the liver
cells. Examination of the central nervous system reveals no particular
changes.
DIVISION II.--PTOMAINES--TOXINES.
§ 648. =Definition of a Ptomaine.=--A ptomaine may be considered as a
basic chemical substance derived from the action of bacteria on
nitrogenous substances. If this definition is accepted, a ptomaine is
not necessarily formed in the dead animal tissue; it may be produced by
the living, and, in all cases, it is the product of bacterial life. A
ptomaine is not necessarily poisonous; many are known which are, in
moderate doses, quite innocuous.
When Selmi’s researches were first published there was some anxiety lest
the existence of ptomaines would seriously interfere with the detection
of poison generally, because some were said to be like strychnine,
others like colchicine, and so forth. Farther research has conclusively
shown that at present no ptomaine is known which so closely resembles a
vegetable poison as to be likely in skilled hands to cause confusion.
Isolation of Ptomaines.
§ 649. =Gautier’s[653] Process.=--The liquid is acidified with oxalic
acid, warmed, filtered, and distilled in a vacuum.
[653] _Ptomaines et Leucomaines_, E. J. A. Gautier, Paris, 1886.
In this way pyrrol, skatol, phenol, indol, and volatile fatty acids are
separated and will be found in the distillate. The residue in the retort
is treated with lime, filtered from the precipitate that forms, and
distilled in a vacuum, the distillate being received in weak sulphuric
acid. The bases accompanied with ammonia distil over. The distillate is
now neutralised by sulphuric acid[654] and evaporated nearly to dryness,
separating the mother liquid from sulphate of ammonia, which
crystallises out. The mother liquids are treated with absolute alcohol,
which dissolves the sulphates of the ptomaines. The alcohol is got rid
of by evaporation, the residue treated with caustic soda, and the bases
shaken out by successive treatment with ether, petroleum ether, and
chloroform. The residue remaining in the retort with the excess of lime
is dried, powdered, and exhausted with ether; the ethereal extract is
separated, evaporated to dryness, the dry residue taken up in a little
water, slightly acidulated, and the bases precipitated by an alkali.
[654] The first acid apparently is so dilute that the distillate more
than neutralises it, hence more sulphuric acid is added to complete
neutralisation.
§ 650. =Brieger’s Process.=--Brieger[655] thus describes his process:--
[655] _Untersuchungen über Ptomaine_, Theil iii., Berlin, 1886.
“The matters are finely divided and boiled with water feebly acidulated
with hydrochloric acid.
“Care must be taken that on boiling, the weak acid reaction must be
retained, and that this manipulation only lasts a few minutes.
[Illustration]
“The insoluble portion is filtered off, and the filtrate evaporated,
either in the gas-oven or on the water-bath, to syrupy consistency. If
the substances are offensive, as alcoholic and watery extracts of flesh
usually are, the use of Bocklisch’s simple apparatus (see diagram) is to
be recommended. The filtrate to be evaporated is placed in a flask
provided with a doubly perforated caoutchouc cork carrying two bent
tubes; the tube _b_ terminates near the bottom of the flask, while the
tube _a_ terminates a little above the level of the fluid to be
evaporated. The tube _a_ is connected with a water pump which sucks away
the escaping steam. In order to avoid the running back of the condensed
water forming in the cooler part of the tube, the end of the tube _a_ is
twisted into a circular form. Through the tube _b_, which has a fine
capillary bore, a stream of air is allowed to enter, which keeps the
fluid in constant agitation, continually destroying the scum on the
surface, and avoiding sediments collecting at the bottom, which may
cause fracture of the flask. According to the regulation of the air
current, a greater or smaller vacuum can be produced. The fluid,
evaporated to the consistency of a syrup, is treated with 96 per cent.
alcohol, filtered, and the filtrate precipitated with lead acetate.
“The lead precipitate is filtered off, the filtrate evaporated to a
syrup, and the syrup again treated with 96 per cent. alcohol. This is
again filtered, the alcohol got rid of by evaporation, water added, the
lead thrown down by SH₂, and the fluid, after the addition of a little
hydrochloric acid, evaporated to the consistence of a syrup; this syrup
is exhausted with 96 per cent. alcohol, and precipitated with an
alcoholic solution of mercury chloride. The mercury precipitate is
boiled with water, and by the different solubility of the mercury salts
of certain ptomaines some separation takes place. If it is suspected
that some of the ptomaines may have been separated with the lead
precipitate, this lead precipitate can be decomposed by SH₂ and
investigated. I have only (says Brieger) in the case of mussels been
able to extract from the lead precipitate small quantities of ptomaines.
“The mercury filtrate is freed from mercury and evaporated, the excess
of hydrochloric acid being carefully neutralised by means of soda (for
it must only be slightly acid); then it is again treated with alcohol,
so as to separate as much as possible the inorganic constituents. The
alcoholic extract is evaporated, dissolved in a little water,
neutralised with soda, acidulated with nitric acid, and precipitated
with phospho-molybdic acid. The phospho-molybdic acid precipitate is
decomposed with neutral lead acetate, which process may be facilitated
by heating on the water-bath. After getting rid of the lead by treatment
with SH₂, the fluid is evaporated to a syrup and alcohol added, by which
process many ptomaines may be eliminated as hydrochlorates; or they can
be converted into double salts (of platinum or gold) for the purpose of
separation. In the filtrate from phospho-molybdate, ptomaines may also
be found by treating with lead acetate to get rid of the
phospho-molybdic acid, and then adding certain reactives. Since it is
but seldom that the hydrochlorates are obtained in a state of purity, it
is preferable to convert the substance separated into a gold or platinum
salt or a picrate, since the greater or less solubility of these
compounds facilitates the purification of individual members; but which
reagent is best to add, must be learned from experience. The
melting-point of these salts must always be taken, so that an idea of
their purity may be obtained. It is also to be noted that many gold
salts decompose on warming the aqueous solution; this may be avoided by
the addition of hydrochloric acid. The hydrochlorates of the ptomaines
are obtained by decomposing the mercury, gold, or platinum combinations
by the aid of SH₂, while the picrates can be treated with hydrochloric
acid and shaken up with ether, which latter solvent dissolves the picric
acid.
“Considerable difficulty in the purification of the ptomaines is caused
by a nitrogenous, amorphous, non-poisonous, albumin-like substance,
which passes into all solutions, and can only be got rid of by careful
precipitation with an alcoholic solution of lead acetate, in which it is
soluble in excess. This albuminoid forms an amorphous compound with
platinum, and acts as a strongly reducing agent (the platinum compound
contains 29 per cent. platinum). When this albuminoid is eliminated,
then the hydrochlorates or the double salts of the ptomaines
crystallise.”
§ 651. =The Benzoyl Chloride Method.=--The fatty diamines in dilute
aqueous solutions, shaken with benzoyl chloride and soda, are converted
into insoluble dibenzoyl derivatives; these may be separated from
benzamide and other nitrogenous products by dissolving the precipitate
in alcohol, and pouring the solution into a large quantity of
water.[656] Compounds which contain two amido groups combined with one
and the same carbon atom, do not yield benzoyl derivatives when shaken
with benzoyl chloride and soda. Hence this reaction can be utilised for
certain of the ptomaines only. The solution must be dilute, because
concentrated solutions of creatine, creatinine, and similar bodies also
give precipitates with benzoyl chloride; no separation, however, occurs
unless these bodies are in the proportion of five per thousand.
[656] L. V. Udrànsky and Baumann, _Ber._, xxi. 2744.
The process is specially applicable for the separation of
ethylenediamine, pentamethylenediamine (cadaverine), and
tetramethylenediamine (putrescine) from urine. In a case of
cystinuria Udrànsky and E. Baumann[657] have found 0·24 grm. of
benzoyltetramethylenediamine, 0·42 grm. of benzoylpentamethylenediamine
in a day. Diamines are absent in normal fæces and urine. Stadthagen and
Brieger[658] have also found, in a case of cystinuria diamines, chiefly
pentamethylenediamine.
[657] L. V. Udrànsky and Baumann, _Zeit. f. physiol. Chem._, xiii. 562.
[658] _Arch. pathol. Anatom._, cxv. p. 3.
The operation is performed by making the liquid alkaline with soda, so
that the alkalinity is equal to about 10 per cent., adding benzoyl
chloride, shaking until the odour of benzoyl chloride disappears, and
then filtering; to the filtrate more benzoyl chloride is added, the
liquid shaken, and, if a precipitate appears, this is also filtered off,
and the process repeated until all diamines are separated.
The precipitate thus obtained is dissolved in alcohol, and the alcoholic
solution poured into a considerable volume of water and allowed to stand
over night; the dibenzoyl compound is then usually found to be in a
crystalline condition. The compound is crystallised once or twice from
alcohol or ether, and its melting-point and properties studied. Mixtures
of diamines may be separated by their different solubilities in ether
and alcohol.
A solution of 0·00788 grm. of pentamethylenediamine in 100 c.c. of water
gave 0·0218 grm. of the dibenzoyl-derivative when shaken with benzoyl
chloride (5 c.c.) and 40 c.c. of soda (10 per cent.) and kept for
twenty-four hours. In a second experiment with a similar solution only
0·0142 grm. of dibenzoyl-derivative was obtained;[659] hence the process
is not a good quantitative process, and, although convenient for
isolation, gives, so far as the total amount recovered is concerned,
varying results.
[659] _Ber._, xxi. 2744.
§ 652. =The Amines.=--The amines are bases originating from ammonia and
built on the same type. Those that are interesting as poisons are
monamines, diamines, and the quaternary ammonium bases.
Considered as compound ammonias, the amines are divided into primary or
amide bases, secondary or imid bases, and tertiary or nitrile bases,
according as to whether one, two, or three atoms of hydrogen have been
displaced from the ammonia molecule by an alkyl; for instance,
methylamine NH₂CH₃ is a primary or amide base, because only one of the
three atoms of H in NH₃ has been replaced by methyl; similarly,
dimethylamine is a secondary or imid base, and trimethylamine is a
tertiary or nitrile base.
The quaternary bases are derived from the hypothetical ammonium
hydroxide NH₄OH, as, for example, tetraethyl ammonium hydroxide
(C₂H₅)₄N,OH.
The diamines are derived from two molecules of NH, and therefore
contain, instead of one molecule of nitrogen, two molecules of nitrogen;
in two molecules of ammonia there are six atoms of hydrogen, two, four,
or six of which may be replaced by alkyls; as, for example,
C₂H₄
/ \
/ \
N--HH--N
\ /
\ /
HH
Ethylenediamine.
C₂H₄
/ \
/ \
N--C₂H₄--N
\ /
\ /
HH
Diethylenediamine.
C₂H₄
/ \
/ \
N--C₂H₄--N
\ /
\ /
C₂H₄
Triethylenediamine.
The monamines are similar to ammonia in their reactions; some of them
are stronger bases; for instance, ethylamine expels ammonia from its
salts. The first members of the series are combustible gases of pungent
odour, and easily soluble in water; the higher homologues are fluids;
and the still higher members solids.
The hydrochlorides are soluble in absolute alcohol, while chloride of
ammonium is insoluble; this property is taken advantage of for
separating amines from ammonia. The amines form double salts with
platinic chloride; this is also utilised for recognition, for the
purpose of separation, and for purification; for instance,
ammonium-platinum-chloride on ignition yields 43·99 per cent. of
platinum, and methylamine-platinum-chloride yields 47·4 of platinum. It
is comparatively easy to ascertain whether an amine is primary,
secondary, or tertiary.
The primary and secondary amines react with nitrous acid, but not the
tertiary; the primary amines, for instance, are converted into alcohols,
and there is an evolution of nitrogen gas; thus methylamine is
decomposed into methyl alcohol, nitrogen, and water.
CH₃NH₂ + (OH)NO = CH₃(OH) + N₂ + H₂O.
The secondary amines, treated in the same way, evolve no nitrogen, but
are converted into nitrosamines; thus dimethylamine, when treated with
nitrous acid, yields nitrosodimethylamine,
(CH₃)₂NH + (OH)NO = (CH₃)₂(NO)N + H₂O;
and the nitrosamines respond to the test known as Lieberman’s
nitroso-reaction, which is thus performed:--The substance is dissolved
in phenol and a few drops of concentrated sulphuric acid added. The
yellow colour at first produced changes into blue by adding to the acid
liquid a solution of potash.
The primary amines, and the primary amines alone, treated with
chloroform and alcoholic potash, yield the peculiarly offensive smelling
carbylamine or isonitrile (Hofmann’s test),