Chapter XXXIII: Part VI: Alkaloids and Poisonous Vegetable Principles Separated for the (7)

§ 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.