[491] A. Ladenburg (Compt. Rend., xc. 92), having succeeded in reproducing atropine by heating tropine and tropic acid with hydrochloric acid, by substituting various organic acids for the tropic acid, has obtained a whole series of compounds to which he has given the name of tropeines. One of these, hydroxytoluol (amygdalic) tropeine, he has named homatropine. It dilates the pupil, but is less poisonous than atropine.
§ 446. Statistics of Atropine Poisoning.—Since atropine is the active principle of belladonna and datura plants, and every portion of these—root, seeds, leaves, and fruit—has caused toxic symptoms, poisoning by any part of these plants, or by their pharmaceutical or other preparations, may be considered with strict propriety as atropine poisoning. Our English death statistics for the ten years ending 1892, record 79 deaths (50 males and 29 females) from atropine (for the most part registered under the head of belladonna); 29 (or 36·7 per cent.) were suicidal, the rest accidental.
The greatest number of the accidental cases arise from mistakes in pharmacy; thus, belladonna leaves have been supplied for ash leaves; the extract of belladonna has been given instead of extract of juniper; the alkaloid itself has been dispensed in mistake for theine;[492] a more curious and marvellously stupid mistake is one in which it was dispensed instead of assafœtida (Schauenstein, op. cit., p. 652). Further, valerianate of atropine has been accidentally substituted for quinine valerianate, and Schauenstein relates a case in which atropine sulphate was administered subcutaneously instead of morphine sulphate; but the result was not lethal. Many other instances might be cited. The extended use of atropine as an external application to the eye naturally gives rise to a few direct and indirect accidents. Serious symptoms have arisen from the solution reaching the pharynx through the lachrymal duct and nose. A curious indirect poisoning, caused by the use of atropine as a collyrium, is related by Schauenstein.[493] A person suffered from all the symptoms of atropine poisoning; but the channel by which it had obtained access to the system was a great mystery, until it was traced to some coffee, and it was then found that the cook had strained this coffee through a certain piece of linen, which had been used months before, soaked in atropine solution, as a collyrium, and had been cast aside as of no value.
§ 447. Accidental and Criminal Poisoning by Atropine.—External applications of atropine are rapidly absorbed, e.g., if the foot of a rat be steeped for a little while in a solution of the alkaloid, and the eyes watched, dilatation of the pupils will soon be observed. If the skin is broken, enough may be absorbed to cause death. A case is on record in which ·21 grm. of atropine sulphate, applied as an ointment to the abraded skin, was fatal.[494] Atropine has also been absorbed from the bowel; in one case, a clyster containing the active principles of 5·2 grms. (80 grains) of belladonna root was administered to a woman twenty-seven years of age, and caused death. Allowing the root to have been carefully dried, and to contain ·21 per cent. of alkaloid, it would seem that so little as 10·9 mgrms. (·16 grain) may even prove fatal, if left in contact with the intestinal mucous membrane. Belladonna berries and stramonium leaves and seeds are eaten occasionally by children. A remarkable series of poisonings by belladonna berries occurred in London during the autumn of 1846.
[494] Ploss, Zeitschr. f. Chir., 1863.
Criminal poisoning by atropine in any form is of excessive rarity in Europe and America, but in India it has been frightfully prevalent. In all the Asiatic cases the substance used has been one of the various species of datura, and mostly the bruised or ground seeds, or a decoction of the seeds. In 120 cases recorded in papers and works on Indian toxicology, I find no less than 63 per cent. of the cases criminal, 19 per cent. suicidal, and 18 per cent. accidental. In noting these figures, however, it must be borne in mind that known criminal cases are more certain to be recorded than any other cases. The drug has been known under the Sanscrit name of dhatoora by the Hindoos from most remote times. It was largely used by the Thugs, either for the purpose of stupefying their victim or for killing him; by loose wives to ensure for a time the fatuity of their husbands; and, lastly, it seems in Indian history to have played the peculiar rôle of a state agent, and to have been used to induce the idiocy or insanity of persons of high rank, whose mental integrity was considered dangerous by the despot in power. The Hindoos, by centuries of practice, have attained such dexterity in the use of the “datura” as to raise that kind of poisoning to an art, so that Dr. Chevers, in his Medical Jurisprudence for India,[495] declares that “there appears to be no drug known in the present day which represents in its effects so close an approach to the system of slow poisoning, believed by many to have been practised in the Middle Ages, as does the datura.”
[495] Dr. Chevers’s work contains a very good history of datura criminal poisoning.
§ 448. Fatal Dose.—It is impossible to state with precision the exact quantity which may cause death, atropine being one of those substances whose effect, varying in different cases, seems to depend on special constitutional tendencies or idiosyncracies of the individual. Some persons take a comparatively large amount with impunity, while others scarcely bear a very moderate dose without exhibiting unpleasant symptoms. Eight mgrms. (1⁄8 grain) have been known to produce poisonous symptoms, and ·129 grm. (2 grains) death. We may, therefore, infer that about ·0648 grm. (1 grain) would, unchecked by remedies, probably act fatally; but very large doses have been recovered from, especially when treatment has been prompt.
Atropine is used in veterinary practice, from 32·4 to 64·8 mgrms. (1⁄2 to 1 grain) and more being administered subcutaneously to horses; but the extent to which this may be done with safety is not yet established.
§ 449. Action on Animals.—The action of atropine has been studied on certain beetles, on reptiles (such as the salamander, triton, frogs, and others), on guinea-pigs, hedgehogs, rats, rabbits, fowls, pigeons, dogs, and cats. Among the mammalia there is no essential difference in the symptoms, but great variation in the relative sensibility; man seems the most sensitive of all, next to man come the carnivora, while the herbivora, and especially the rodents, offer a considerable resistance. According to Falck the lethal dose for a rabbit is at least ·79 mgrm. per kilo. It is the general opinion that rabbits may eat sufficient of the belladonna plant to render their flesh poisonous, and yet the animals themselves may show no disturbance in health; but this must not be considered adequately established. Speaking very generally, the higher the animal organisation the greater the sensibility to atropine. Frogs are affected in a peculiar manner. According to the researches of Fraser,[496] the animal is first paralysed, and some hours after the administration of the poison lies motionless, the only signs of life being the existence of a slight movement of the heart and muscular irritability. After a period of from forty-eight to seventy-two hours, the fore limbs are seized with tetanic spasms, which develop into a strychnine-like tetanus.
[496] Transact. of Edin. Roy. Soc., vol. xxv. p. 449. Journ. of Anat. and Physiol., May 1869, p. 357.
§ 450. Action on Man.—When atropine is injected subcutaneously, the symptoms, as is usually the case with drugs administered in this manner, may come on immediately, the pupil not unfrequently dilating almost before the injection is finished. This is in no way surprising; but there are instances in which decoctions of datura seeds have been administered by the stomach, and the commencement of symptoms has been as rapid as in poisoning by oxalic or even prussic acid. In a case tried in India in July 1852, the prosecutor declared that, while a person was handing him a lota of water, the prisoner snatched it away on pretence of freeing the water from dirt or straws, and then gave it to him. He then drank only two mouthfuls, and, complaining of the bitter taste, fell down insensible within forty yards of the spot where he had drunk, and did not recover his senses until the third day after. In another case, a man was struck down so suddenly that his feet were scalded by some hot water which he was carrying.—Chevers.
When the seeds, leaves, or fruit of atropine-holding plants are eaten, there is, however, a very appreciable period before the symptoms commence, and, as in the case of opium poisoning, no very definite rule can be laid down, but usually the effects are experienced within half an hour. The first sensation is dryness of the mouth and throat; this continues increasing, and may rise to such a degree that the swallowing of liquids is an impossibility. The difficulty in swallowing does not seem to be entirely dependent on the dry state of the throat, but is also due to a spasmodic contraction of the pharyngeal muscles. Tissore[497] found in one case such constriction that he could only introduce emetics by passing a catheter of small diameter. The mucous membrane is reddened, and the voice hoarse.[498] The inability to swallow, and the changed voice, bear some little resemblance to hydrophobia—a resemblance heightened to the popular mind by an inclination to bite, which seems to have been occasionally observed; the pupils are early dilated, and the dilatation may be marked and extreme; the vision is deranged, letters and figures often appear duplicated; the eyeballs are occasionally remarkably prominent, and generally congested; the skin is dry, even very small quantities of atropine arresting the cutaneous secretion; in this respect atropine and pilocarpine are perfect examples of antagonism. With the dryness of skin, in a large percentage of cases, occurs a scarlet rash over most of the body. This is generally the case after large doses, but Stadler saw the rash produced on a child three months old by ·3 mgrm. of atropine sulphate. It appeared three minutes after the dose, lasted five hours, and was reproduced by a renewed dose.[499] The temperature of the body with large doses is raised; with small, somewhat lowered. The pulse is increased in frequency, and is always above 100—mostly from 115 to 120, or even 150, in the minute. The breathing is at first a little slowed, and then very rapid. Vomiting is not common; the sphincters may be paralysed so that the evacuations are involuntary, and there may be also spasmodic contractions of the urinary bladder. The nervous system is profoundly affected; in one case there were clonic spasms,[500] in another,[501] such muscular rigidity, that the patient could with difficulty be placed on a chair. The lower extremities are often partly paralysed, there is a want of co-ordination, the person reels like a drunken man, or there may be general jactitation. The disturbance of the brain functions is very marked; in about 4 per cent. only of the recorded cases has there been no delirium, or very little—in the majority delirium is present. In adults this generally takes a garrulous, pleasing form, but every variety has been witnessed. Dr. H. Giraud describes the delirium from datura (which it may be necessary to again repeat is atropine delirium) as follows:—“He either vociferates loudly or is garrulous, and talks incoherently; sometimes he is mirthful, and laughs wildly, or is sad and moans, as if in great distress; generally he is observed to be very timid, and, when most troublesome and unruly, can always be cowed by an angry word, frequently putting up his hands in a supplicating posture. When approached he suddenly shrinks back as if apprehensive of being struck, and frequently he moves about as if to avoid spectra. But the most invariable accompaniment of the final stage of delirium, and frequently also that of sopor, is in the incessant picking at real or imaginary objects. At one time the patient seizes hold of parts of his clothes or bedding, pulls at his fingers and toes, takes up dirt and stones from the ground, or as often snatches at imaginary objects in the air, on his body, or anything near him. Very frequently he appears as if amusing himself by drawing out imaginary threads from the ends of his fingers, and occasionally his antics are so varied and ridiculous, that I have seen his near relatives, although apprehensive of danger, unable to restrain their laughter.”[502] This active delirium passes into a somnolent state with muttering, catching at the bedclothes, or at floating spectra, and in fatal cases the patient dies in this stage. As a rule, the sleep is not like opium coma; there is complete insensibility in both, but in the one the sleep is deep, without muttering, in the other, from atropine, it is more like the stupor of a fever. The course in fatal cases is rapid, death generally taking place within six hours. If a person live over seven or eight hours, he usually recovers, however serious the symptoms may appear. On waking, the patient remembers nothing of his illness; mydriasis remains some time, and there may be abnormality of speech and weakness of the limbs, but within four days health is re-established. In cases where the seeds have been swallowed, the symptoms may be much prolonged, and they seem to continue until all the seeds have been voided—perhaps this is due to the imperfect but continuous extraction of atropine by the intestinal juices.
[497] Gaz. hebd., 1856.
[498] A friend of the author’s was given, by a mistake in dispensing, 16 minims of a solution of atropine sulphate, equivalent to 1⁄7 grain of atropine (or 9·3 mgrms). Ten minutes after taking the dose there was dilatation of the pupil, indistinctness of vision, with great dryness of the throat and difficulty in swallowing; he attempted to eat a biscuit, but, after chewing it, he was obliged to spit it out, as it was not possible to swallow; the throat was excessively sore, and there was a desire to pass urine, but only a few drops could be voided. In forty-five minutes he was unable to stand or walk. There was a bright rash on the chest. In two hours he became insensible, and was taken to the Middlesex Hospital, recovering under treatment in about eight hours.
[499] Med. Times, 1868.
[500] Lancet, vol. i., 1881, p. 414.
[501] Ibid., vol. i., 1876, p. 346.
[502] In an English case of belladonna poisoning, the patient, a tailor, sat for four hours, moving his hands and arms as if sewing, and his lips as if talking, but without uttering a word.
Chronic poisoning by atropine may, from what has been stated, be of great importance in India. It is probable that its continuous effect would tend to weaken the intellect, and there is no reason for any incredulity with regard to its power as a factor of insanity. Rossbach has ascertained that if dogs are, day after day, dosed with atropine, they become emaciated; but a certain tolerance is established, and the dose has to be raised considerably after a time to produce any marked physiological effect.
§ 451. Physiological Action of Atropine.—From the numerous experiments on animals which have been performed for the purpose of elucidating the action of atropine, it is clear that the terminations of the vagus in the heart muscle are first excited, and then paralysed. The excitor-motor ganglion is also paralysed, and finally the heart itself; death resulting from heart paralysis. The respiratory disturbance is also to be ascribed to the vagus; the terminations in the lung are paralysed, and, at the same time, the poison circulating through the respiratory nervous centre stimulates it first, and then it also becomes finally paralysed. The small vessels are generally widened after a previous transitory narrowing. Organs containing unstriped muscular fibre are generally paralysed, as well as the ends of the nerves regulating secretion—hence the dryness of the skin. The action on the iris is not thoroughly elucidated.
§ 452. The diagnosis of atropine poisoning may be very difficult unless the attention of the medical man be excited by some suspicious circumstance. A child suffering from belladonna rash, with hot dry skin, quick pulse, and reddened fauces, looks not unlike one under an attack of scarlet fever. Further, as before mentioned, some cases are similar to rabies; and again, the garrulous delirium and the hallucinations of an adult are often very similar to those of delirium tremens, as well as tomania.
§ 453. Post-mortem Appearances.—The post-mortem appearances do not seem to be characteristic, save in the fact that the pupils remain dilated. The brain is usually hyperæmic, and in one case the absence of moisture seems to have been remarkable. The stomach and intestines may be somewhat irritated if the seeds, leaves, or other parts of the plant have been eaten; but the irritation is not constant if the poisoning has been by pure atropine, and still less is it likely to be present if atropine has been administered subcutaneously.
§ 454. Treatment.—The great majority of cases recover under treatment. In 112 cases collected by F. A. Falck, 13 only were fatal (11·6 per cent.). The greater portion of the deaths in India are those of children and old people—persons of feeble vitality. The Asiatic treatment, which has been handed down by tradition, is the application of cold water to the feet; but the method which has found most favour in England is treatment by pilocarpine, a fifth of a grain or more being injected from time to time. Pilocarpine shows as perfect antagonism as possible; atropine dries, pilocarpine moistens the skin; atropine accelerates, pilocarpine slows the respiration. Dr. Sydney Ringer and others have published a remarkable series of cases showing the efficacy of this treatment, which, of course, is to be combined where necessary with emetics, the use of the stomach-pump, &c.[503]
[503] See, for Dr. Ringer’s cases, Lancet, vol. i., 1876, p. 346. Refer also to Brit. Med. Journ., vol. i., 1881, p. 594; ib., p. 659.
§ 455. Separation of Atropine from Organic Tissues, &c.—From the contents of the stomach, atropine may be separated by acidulating strongly with sulphuric acid (15 to 20 c.c. of dilute H2SO4 to 100 c.c.), digesting for some time at a temperature not exceeding 70°, and then reducing any solid matter to a pulp by friction, and filtering, which can generally be effected by the aid of a filter-pump. The liver, muscles,[504] and coagulated blood, &c., may also be treated in a precisely similar way. The acid liquid thus obtained, is first, to remove impurities, shaken up with amyl alcohol, and after the separation of the latter in the usual manner, it is agitated with chloroform, which will take up any of the remaining amyl alcohol,[505] and also serve to purify further. The chloroform is then removed by a pipette (or the separating flask before described), and the fluid made alkaline, and shaken up with ether, which, on removal, is allowed to evaporate spontaneously. The residue will contain atropine, and this may be farther purified by converting it into oxalate, as suggested, page 374.
[504] Neither amyl alcohol nor chloroform removes atropine from an acid solution.
[505] Atropine goes into the blood, and appears to be present in the different organs in direct proportion to the quantity of blood they contain. Dragendorff has found in the muscles of rabbits fed upon belladonna sufficient atropine for quantitative estimation.
From the urine,[506] atropine may be extracted by acidifying with sulphuric acid, and agitation with the same series of solvents. Atropine has been separated from putrid matters long after death, nor does it appear to suffer any decomposition by the ordinary analytical operations of evaporating solutions to dryness at 100°. In other words, there seems to be no necessity for operations in vacuo, in attempts at separating atropine.
[506] Dragendorff has found atropine in the urine of rabbits fed with belladonna; the separation by the poison is so rapid that it often can only be recognised in the urine during the first hour after the poison has been taken.
TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE HENBANE PLANT.
| Plant Destitute of Flowers. | Plant in Flower. | Plant in Fruit. | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hyosc.- Albus. |
Hyosc.- Niger. |
Hyosc.- Albus. |
Hyosc.- Niger. |
Hyosc.- Albus. |
Hyosc.- Niger. |
|||||||
| 1868. | 1869. | 1868. | 1869. | 1868. | 1869. | 1868. | 1869. | 1868. | 1869. | 1868. | 1869. | |
| Seeds, | ... | ... | ... | ... | ... | ... | ... | ... | 0·162 | 0·172 | 0·075 | 0·118 |
| Leaves, | 0·588 | 0·469 | 0·154 | 0·192 | 0·359 | 0·329 | 0·147 | 0·206 | 0·211 | 0·153 | 0·065 | 0·110 |
| Stalk, | 0·012 | ... | 0·070 | 0·017 | 0·036 | 0·048 | 0·032 | 0·030 | 0·027 | 0·029 | 0·009 | 0·010 |
| Root, | 0·128 | 0·176 | 0·027 | 0·080 | 0·146 | 0·262 | 0·127 | 0·138 | 0·106 | 0·086 | 0·028 | 0·056 |
§ 456. This powerful alkaloid is contained in small quantities in datura and belladonna, and also is found in the common lettuce (·001 per cent.),[507] and in Scopola carmolica, a solanaceous plant indigenous to Austria and Hungary[508]; but its chief source is the Hyoscyamus niger and Hyoscyamus alba (black and white henbane): it is also found in the Duboisia myoporoides. The latter plant was considered to contain a new alkaloid, “Duboisine,” but duboisine is a mixture of hyoscyamine and hyoscine. Ladenburg’s hyoscine accompanies hyoscyamine, and is an isomeride of both atropine and hyoscyamine; its chemical reactions are similar to those of hyoscyamine, as well as its physiological effects.[509]
[507] T. S. Dymond, Journ. Chem. Soc. Trans., 1892, 90.
[508] W. R. Dunstan and A. E. Chaston. Pharm. Journ. Trans. (3), xx. 461-464.
[509] See Ber. der deutsch. Chem. Gesell., 13, 1549 to 1554. By boiling hyoscine hydrochloride with animal charcoal, and then precipitating with auric chloride, a good crystalline compound, melting at 198°, can be obtained.
Hyoscyamine (C17H23NO3), as separated in the course of analysis, is a resinoid, sticky, amorphous mass, difficult to dry, and possessing a tobacco-like odour. It can, however, be obtained in well-marked odourless crystals, which melt at 108°-109°, a portion subliming unchanged. It liquefies under boiling water without crystallisation. According to Thorey,[510] hyoscyamine crystallises out of chloroform in rhombic tables, and out of benzene in fine needles; but out of ether or amyl alcohol it remains amorphous. When perfectly pure, it dissolves with difficulty in cold, but more readily in hot, water; if impure, it is hygroscopic, and its solubility is much increased. In any case, it dissolves easily in alcohol, ether, chloroform, amyl alcohol, benzene, and dilute acids. Hyoscyamine neutralises acids fully, and forms crystallisable salts, which assume for the most part the form of needles. It is isomeric with atropine, and is converted into atropine by heating to 110°, or warming with alcoholic potash. The gold salt melts at 159°, and does not melt in boiling water like the atropine gold salt.
[510] Pharm. Zeitschr. f. Russl., 1869.
§ 457. Pharmaceutical and other Preparations of Henbane.—The leaves are alone officinal in the European pharmacopœias; but the seeds and the root, or the flowers, may be met with occasionally, especially among herbalists. The table[511] (p. 382) will give an idea of the alkaloidal content of the different parts of the plant.
[511] This table, taken from Dragendorff’s Chemische Werthbestimmung einiger starkwirkenden Droguen, embodies the researches of Thorey.
In order to ascertain the percentage of the alkaloid in any part of the plant, the process followed by Thorey has the merit of simplicity. The substance is first exhausted by petroleum ether, which frees it from fat; after drying, it is extracted with 85 per cent. alcohol at a temperature not exceeding 40°. The alcoholic extracts are then united, the alcohol distilled off, and the residue filtered. The filtrate is now first purified by agitation with petroleum ether, then saturated by ammonia, and shaken up with chloroform. The latter, on evaporation, leaves the alkaloid only slightly impure, and, after washing with distilled water, if dissolved in dilute sulphuric acid, a crystalline sulphate may be readily obtained.
A tincture and an extract of henbane leaves and flowering tops are officinal in most pharmacopœias; an extract of the seeds in that of France.
An oil of hyoscyamus is officinal in all the Continental pharmacopœias, but not in the British.
Henbane juice is recognised by the British pharmacopœia; it is about the same strength as the tincture.
An ointment, made of one part of the extract to nine of simple ointment, is officinal in the German pharmacopœia.
The tincture (after distilling off the spirit) and the extracts (on proper solution) may be conveniently titrated by Mayer’s reagent (p. 263), which, for this purpose, should be diluted one-half; each c.c. then, according to Dragendorff, equalling 6·98 mgrms. of hyoscyamine. Kruse found 0·042 per cent. of hyoscyamine in a Russian tincture, and ·28 per cent. in a Russian extract. Any preparation made with extract of henbane will be found to contain nitrate of potash, for Attfield has shown the extract to be rich in this substance. The ointment will require extraction of the fat by petroleum ether; this accomplished, the determination of its strength is easy.
The oil of hyoscyamus is poisonous, and contains the alkaloid. An exact quantitative research is difficult; but if 20 grms. of the oil are shaken up for some time with water acidified by sulphuric acid, the fluid separated from the oil, made alkaline, shaken up with chloroform, and the latter removed and evaporated, sufficient will be obtained to test successfully for the presence of the alkaloid, by its action on the pupil of the eye.
§ 458. Dose and Effects.—The dose of the uncrystalline hyoscyamine is 6 mgrms. (1⁄10 grain), carefully increased. I have seen it extensively used in asylums to calm violent or troublesome maniacs. Thirty-two mgrms. (1⁄2 grain) begin to act within a quarter of an hour; the face flushes, the pupils dilate, there is no excitement, all muscular motion is enfeebled, and the patient remains quiet for many hours, the effects from a single dose not uncommonly lasting two days. 64·8 mgrms. (1 grain) would be a very large, and possibly fatal, dose. The absence of delirium or excitement, with full doses of hyoscyamine, is a striking contrast to the action of atropine, in every other respect so closely allied; yet there are cases on record showing that the henbane root itself has an action similar to that of belladonna, unless indeed one root has been mistaken for another; e.g., Sonnenschein relates the following ancient case of poisoning:—In a certain cloister the monks ate by error the root of henbane. In the night they were all taken with hallucinations, so that the pious convent was like a madhouse. One monk sounded at midnight the matins, some who thereupon came into chapel could not read, others read what was not in the book, others sang drinking songs—in short, there was the greatest disturbance.
§ 459. Separation of Hyoscyamine from Organic Matters.—The isolation of the alkaloid from organic tissues or fluids, in cases where a medicinal preparation of henbane, or of the leaves, root, &c., has been taken, is possible, and should be carried out on the principles already detailed. Hyoscyamine is mainly identified by its power of dilating the pupil of the eye. It is said that so small a quantity as ·0083 mgrm. (1⁄4000 grain) will in fifteen minutes dilate the eye of a rabbit. It is true that atropine also dilates the pupil; but if sufficient of the substance should have been isolated to apply other tests, it can be distinguished from atropine by the fact that the latter gives no immediate precipitate with platinic chloride, whilst hyoscyamine is precipitated by a small quantity of platinic chloride, and dissolved by a larger amount, and also by the characters of the gold salt.
§ 460. Hyoscine, C17H23NO3.—According to E. Schmidt[512] the formula is C17H21NO4 + H2O, and the alkaloid is identical with scopolamine. Scopolamine has a m.p. of 59°, gives an aurochloride, crystallising in needles, the m.p. of which is 212° to 214°; when boiled with baryta water, it splits up into atropic acid and scopoline, a base (C8H13NO), m.p. 110°, boiling-point, 241° to 243°; scopoline forms an aurochloride, m.p. 223°-225°; and a platinochloride, m.p. 228°-230°; but Ladenburg,[513] in answer to Schmidt, asserts that hyoscine exists, and is not identical with scopolamine. A sample of commercial hyoscine hydrobromide Nagelvoort found to melt, water-free, at 198°; other commercial samples of hydrobromide melted at 179° and 186°; the latter sample giving an aurochloride which melted at 192°. Pure hyoscine gold chloride is stated to melt at 198°. Its reactions are much the same as those of atropine, but it does not blacken calomel. It is very poisonous.
According to experiments on animals, the heart is first slowed, then quickened; the first effect being due to a stimulation of the inhibitory nervous apparatus, the second to a paralysing action on the same. The temperature is not altered. The pupils are dilated, the saliva diminished. The irritability of the brain is lessened.[514]
[514] Parloff, St Petersburg Med. Chem. Acad., Dissert. No. 9, 1889-90.
§ 461. Distribution of Solanine.—Solanine is a poisonous nitrogenised glucoside found in all parts of the plants belonging to the nightshade order. The English common plants in which solanine occurs are the edible potato plant (Solanum tuberosum), the nightshade (Solanum nigrum), and the Solanum dulcamara, or bitter-sweet. The berries of the Solanum nigrum and those of S. dulcamara contain about 0·3 per cent. Mature healthy potatoes appear to contain no solanine, but from 150 grms. of diseased potatoes G. Kassner[515] separated 30 to 50 mgrms.
[515] Arch. Pharm. (3), xxv. 402, 403.
R. Firbas,[516] in a research on the active substances or young shoots of the S. tuberosum found two products—one crystalline, Solanine; the other amorphous, Solaneine. He gives the following formula to solanine—C52H93NO1841⁄2H2O; when dried at 100° it becomes anhydrous. From a solution in 85 per cent. alcohol it crystallises in colourless needles, m.p. 244°; these are almost insoluble in ether and alcohol, but are readily dissolved in dilute hydrochloric acid. On hydrolysis solanine breaks up into solanidine and a sugar, according to the equation—
C52H93NO18 = C40H61NO2 + 2C6H12O6 + 4H2O.
[516] Monatsh., x. 541-560; Journ. Chem. Soc. (Abst.), Jan. 1890.
§ 462. Properties of Solanine.—The reaction of the crystals is weakly alkaline; the taste is somewhat bitter and pungent. Solanine is soluble in 8000 parts of boiling water, 4000 parts of ether, 500 parts of cold, and 125 of boiling alcohol. It dissolves well in hot amyl alcohol, but is scarcely soluble in benzene. An aqueous solution froths on shaking, but not to the degree possessed by saponine solutions.
The amyl alcohol solution has the property of gelatinising when cold. It does this if even so little as 1 part of solanine is dissolved in 2000 of hot amyl alcohol. The jelly is so firm that the vessel may be inverted without any loss. This peculiar property is one of the most important tests for the presence of solanine. The hot ethylic alcohol solution will, on cooling, also gelatinise, but a stronger solution is required. From very dilute alcoholic solutions (and especially with slow cooling) solanine may be obtained in crystals. In dilute mineral acids solanine dissolves freely, and forms salts, which for the most part have an acid reaction and are soluble in alcohol and in water, but with difficulty in ether. The compounds with the acids are not very stable, and several of them are broken up on warming the solution, solanine separating out from the aqueous solutions of the solanine salts. The alkaloid may be precipitated by the fixed and volatile alkalies, and by the alkaline earths. Solanine will stand boiling with strongly alkaline solutions without decomposition; but dilute acids, on warming, hydrolyse. By heating solanine in alcoholic solution with ethyl iodide in closed tubes, and then treating the liquid with ammonia, ethyl solanine in well-formed crystals can be obtained. Solanine is precipitated by phosphomolybdic acid, but by very few other substances. It gives, for example, no precipitate with the following reagents:—Platinic chloride, gold chloride, mercuric chloride, potassic bichromate, and picric acid. Tannin precipitates it only after a time. Sodic phosphate gives a crystalline precipitate of solanine phosphate, if added to a solution of solanine sulphate. Both solanine and solanidine give with nitric acid at first a colourless solution, which, on gentle warming, passes into blue, then into light red, and lastly becomes weakly yellow. Solanine, dissolved in strong sulphuric acid, to which a little Fröhde’s reagent is added, at first colours the fluid light brown; after standing some time the edges of the drop becomes reddish-yellow, and finally the whole a beautiful cherry-red, which gradually passes into dark violet when violet-coloured flocks separate.
§ 463. Solanidine.—Solanidine has stronger basic properties than solanine. Its formula is C40H61NO2. It is obtained from an alcoholic solution in amorphous masses interspersed with needles; m.p. 191°. It dissolves readily in hot alcohol, with difficulty in ether. With hydrochloric acid it forms a hydrochloride—3(C40H61NO2HCl)HCl + H2O or 11⁄2H2O. This hydrochloride is a slightly yellow powder, only sparingly soluble in water, and carbonising without melting when heated to 287°. Solanidine also forms a sulphate, 3(C40H61NO2H2SO4)H2SO4 + 8H2O; this salt is in the form of scaly plates, melting at 247°; it dissolves readily in water.
The sugar obtained from the hydrolysis of solanidine is a yellow amorphous mass dissolving readily in water and wood spirit, and has a specific rotatory power of [α]D = + 28·623. With Phenylhydrazine hydrochloride and sodium acetate in aqueous solution it forms a glucosazone, melting at 199°. It is probably a mixture of sugars.
Solaneine is the name that has been given to the amorphous substance accompanying solanine; on hydrolysis it yields solanidine and the same sugar as solanine. Its formula is C52H82NO13 with 4H2O.
§ 464. Poisoning from Solanine.—Poisoning from solanine has been, in all recorded cases, induced, not by the pure alkaloid (which is scarcely met with out of the laboratory of the scientific chemist), but by the berries of the different species of Solanum, and has for the most part been confined to children. The symptoms in about twenty cases,[517] which may be found detailed in the medical literature of this century, have varied so greatly that the most opposite phenomena have been witnessed as effects of poisoning by the same substance. The most constant phenomena are a quick pulse, laboured respiration, great restlessness, and hyperæsthesia of the skin. Albumen in the urine is common. Nervous symptoms, such as convulsions, aphasia, delirium, and even catalepsy, have been witnessed. In some cases there have been the symptoms of an irritant poison—diarrhœa, vomiting, and pain in the bowels: in many cases dilatation of the pupil has been observed.