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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.

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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.

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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]

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§ 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]

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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:—

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TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE BELLADONNA PLANT.

	Quantity of Alkaloids in the Fresh Substance, per cent.				Quantity of Alkaloids in the Dry Substance, per cent.
	(a.) By Weighing.		(b.) By Titration.		(a.) By Weighing.		(b.) By 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]

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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.

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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 Datura.	Seeds of Capsicum.
(1.) Outline angular.	Outline rounded.
(2.) Attached to the placenta by a large, white, fleshy mass separating easily, leaving a deep furrow along half the length of the seed’s concave border.	Attached to the placenta by a cord from a prominence on the concave border of the seed.
(3.) Surface scabrous, almost reticulate, except on the two compressed sides, where it has become almost glaucous from pressure of the neighbouring seeds.	Uniformly scabrous, the sides being equally rough with the borders.
(4.) Convex border thick and bulged with a longitudinal depression between the bulgings, caused by the compression of the two sides.	Convex border thickened, but uniformly rounded.
(5.) A suitable section shows the embryo curved and twisted in the fleshy albumen.	The embryo, exposed by a suitable section, is seen to resemble in outline very closely the figure 6.
(6.) The taste of the datura seeds is very feebly bitter. The watery decoction causes dilatation of the pupil.	The taste of capsicum is pungent; a decoction irritates the eye much, but does not cause dilatation of the pupil.

The identity of the active principle in both the datura and belladonna tribes is now completely established.[486]

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§ 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.

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(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.

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(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.:—

Tropic acid

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—

Atropine

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.

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On chemical treatment of the viscera, a mixture of alkaloids was obtained which did not give either the reactions of strychnine or of atropine. To test the possibility of these alkaloids obscuring each other’s reactions, mixtures of 3 per cent. solutions (the strength of the injections) of atropine sulphate and strychnine nitrate were mixed together, and strychnine tested for by the dichromate and sulphuric acid test.

A mixture of equal parts gave the strychnine reaction very clearly, but the atropine reaction not at all; 1 strychnine with 3 of atropine gave strychnine reaction, but not that of atropine; 1 strychnine with 4 atropine gave indistinct reaction for both alkaloids; 1 of strychnine with 5 of atropine gave a momentary atropine reaction, the violet was, however, almost immediately replaced by a red colour. Vitali’s reaction was not clearly shown until the mixture was in the proportion of 9 of atropine to 1 of strychnine, but mixtures in the proportion of 3 strychnine and 1 atropine will give distinct mydriasis.

In such a case, of course, the strychnine should be separated from the atropine; this can be effected by precipitating the strychnine as chromate, filtering and recovering from the filter the atropine by alkalising and shaking it out with ether.

The atropine may be farther purified by converting it into oxalate, dissolving the oxalate in as small a quantity of alcohol as possible, and precipitating the oxalate out with ether; the precipitate is collected, dissolved in as small a quantity of water as possible, the water made alkaline, and the base shaken out with ether.

The most reliable test for atropine, or one of the mydriatic alkaloids, is its action on the iris; a solution of atropine, even so weak as 1 : 130,000, causing dilatation.[489] This action on the iris has been studied by Ruyter,[490] Donders, and von Graefe.

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The action is local, taking effect when in dilute solution only on the eye to which it has been applied; and it has been produced on the eyes of frogs, not only in the living subject, but after the head has been severed from the body and deprived of brain. The thinner the cornea, the quicker the dilatation; therefore, the younger the person or animal, the more suitable for experiment. In frogs, with a solution of 1 : 250, dilatation commences in about five minutes; in pigeons, seven minutes; and in rabbits, ten minutes. In man, a solution of 1 : 120 commences to act in about six to seven minutes, reaches its highest point in from ten to fifteen minutes, and persists more or less for six to eight days. A solution of 1 : 480 acts first in fifteen to twenty minutes, and reaches its greatest point in twenty minutes; a solution of 1 : 48,000 requires from three-quarters of an hour to an hour to show its effect. Dogs and cats are far more sensible to its influence than man, and therefore more suitable for experiment. If the expert chooses, he may essay the proof upon himself, controlling the dilatation by Calabar bean; but it is seldom necessary or advisable to make personal trials of this nature.[491]

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