[564] Rhen. West. Corr. Bl., 15, 1848; Husemann in Maschka’s Handbuch.
In the cumulative form, the symptoms may suddenly burst out, and the person pass into death in a fainting-fit without any warning. As a rare effect, hemiplegia may be mentioned.
This brief résumé of the symptoms may be further illustrated by the following typical cases:—A recruit, aged 22, desiring to escape from military service, went to a so-called “Freimacher” who gave him 100 pills, of which he was to take eight in two doses daily. Eleven days after the use of the pills, he became ill, and was received into hospital, where he suddenly died after three weeks’ treatment. His malady was at first ascribed to gastric catarrh; for he suffered from loss of appetite, nausea, and constipation. He complained of pain in the head, and giddiness. His breath smelled badly, and the region of the stomach was painful on pressure. The pulse was slow (56), the temperature of the body normal. Towards the end, the pulse sank to 52; he suffered from vomiting, noise in the ears, troubles of vision, great weakness, and later, hiccough and swelling in the neck. The mere act of standing up in order to show his throat caused him to faint; on the same day on which this occurrence took place, he suddenly died on the way to the nightstool. Thirteen of the pills were found in the patient’s clothes, and from a chemical and microscopical examination it was found that they contained digitalis leaf in fine powder. The quantity which the unfortunate man took in the four weeks was estimated at 13·7 grms. (= about 211 grains).
Two of his comrades had also been to the “Freimacher,” and had suffered from the same symptoms, but they had left off the use of the medicine before any very serious effect was produced.[565][566]
[565] Köhnhorn, Vierteljahrsschr. f. ger. Med., 1876, n. F. xxiv. p. 402.
[566] There is an interesting case on record, in which a woman died from the expressed juice of digitalis. She was twenty-seven years of age, and took a large unknown quantity of the freshly expressed juice for the purpose of relieving a swelling of the limbs. The symptoms came on almost immediately, she was very sick, and was attacked by a menorrhagia. These symptoms continued for several days with increasing severity, but it was not until the fifth day that she obtained medical assistance. She was then found semi-comatose, the face pale, pulse slow, epigastrium painful on pressure, diarrhœa, and hiccough were frequent. She died on the twelfth day. The post-mortem appearances showed nothing referable to digitalis save a few spots of inflammation on the stomach.—Caussé, Bull. de Thérapeutique, vol. lvi. p. 100; Brit. and For. Med. Chir. Review, vol. xxvi., 1860, p. 523.
An instructive case of poisoning by digitoxin occurred in the person of Dr. Koppe, in the course of some experiments on the drug. He had taken 1·5 mgrm. in alcohol without result; on the following day (May 14) he took 1 mgrm. at 9 A.M., but again without appreciable symptoms. Four days later he took 2 mgrms. in alcoholic solution, and an hour afterwards felt faint and ill, with a feeling of giddiness; the pulse was irregular, of normal frequency, 80 to 84. About three hours after taking the digitoxin, Dr. Koppe attempted to take a walk, but the nausea, accompanied with a feeling of weakness, became so intense that he was obliged to return to the house. Five hours after the dose, his pulse was 58, intermittent after about every 30 to 50 beats. Vomiting set in, the matters he threw up were of a dark green colour; after vomiting he felt better for a quarter of an hour, then he again vomited much bilious matter; the pulse sank to 40, and was very intermittent, stopping after every 2 or 3 beats. Every time there was an intermission, he felt a feeling of constriction and uneasiness in the chest. Six and a quarter hours after the dose there was again violent vomiting and retching, with paleness of the face. The muscular weakness was so great that he could not go to bed without assistance. He had a disorder of vision, so that the traits of persons well-known to him were changed, and objects had a yellow tint. He had a sleepless night, the nausea and vomiting continuing. During the following day the symptoms were very similar, and the pulse intermittent, 54 per minute. He passed another restless night, his short sleep being disturbed by terrible dreams. On the third day he was somewhat better, the pulse was 60, but irregular and still intermittent; the nausea was also a little abated. The night was similar in its disturbed sleep to the preceding. He did not regain his full health for several days.[567]
[567] Arch. f. exp. Path. u. Pharm., vol. iii. p. 289, 1875.
A third case may be quoted, which differs very markedly from the preceding, and shows what a protean aspect digitalin poisoning may assume. A woman, twenty-three years old, took on June 26th, at 7 A.M., for the purpose of suicide, 16 granules of digitalin. Two hours later there was shivering and giddiness, so that she was obliged to go to bed. In the course of the day she had hallucinations. In the evening at 8 P.M., after eating a little food, she had a shivering fit so violent that her teeth chattered; there was cold sweat, and difficulty in breathing; she became gradually again warm, but could not sleep. At 1 A.M. the difficulty of breathing was so great that she dragged herself to the window, and there remained until 3 A.M., when she again went back to bed, slept until 7 A.M., and woke tolerably well. Since this attempt of self-destruction had failed, she took 40 granules. After one hour she became giddy, had hallucinations, chilliness, cold sweats, copious vomiting, and colicky pains; there was great muscular weakness, but no diarrhœa. Towards evening the vomiting became worse. There was no action of the bowels, nor was any urine passed; she felt as if her eyes were prominent and large. The sufferings described lasted during the whole night until five o’clock the following day, when the vomiting ceased, whilst the hallucinations, chilliness, and cold sweat continued; and the thirst, sick feeling, and weakness increased. The next morning, a physician found her motionless in bed, with pale face, notable double exophthalmus, dilated pupils, and cold skin, covered with sweat; the pulse was small and intermittent, sometimes scarcely to be felt (46 to 48 per minute); the epigastrium was painful on pressure. She passed this second night without sleep, and in the morning the pulse had risen from 56 to 58 beats, but was not quite so intermittent. There was some action of the bowels, but no urine was passed, nor had any been voided from the commencement; the bladder was not distended. The following (third) day some red-coloured, offensive urine was passed; the skin was warmer, and the pulse from 60 to 64, still somewhat intermittent—from this time she began to improve, and made a good recovery.[568]
[568] Related by Ducroix: De l’Empoisonnement par la Digitale et la Digitaline. Paris, 1864.
§ 540. Physiological Action of the Digitalins.—Whatever other physiological action this group may have, its effect on the heart’s action is so prominent and decided, that the digitalins stand as a type of heart poisons. The group of heart poisons has been much extended of late years, and has been found to include the following:—Antiarin, an arrow poison; helleborin, a glucoside contained in the hellebore family; a glucoside found in the Apocynaceæ, Thevatii neriifolia, and Thevatia iccotli; the poisonous principle of the Nerium oleander and N. odorum; the glucoside of Tanghinia venenifera; convallamarin, derived from the species of Convallaria; scillotoxin, from the squill; superbin, from the Indian lily; and the alkaloid erythrophlœin from the Erythrophlœum judiciale (see p. 432 et seq.). This list is yearly increasing.
§ 541. Local Action.—The digitalins have an exciting or stimulating action if applied to mucous membranes—e.g., if laid upon the nasal mucous surface, sneezing is excited; if applied to the eye, there is redness of the conjunctivæ with smarting; if to the tongue, there is much irritation and a bitter taste. The leaves, the extract, and the tincture all have this directly irritating action, for they all redden and inflame mucous membranes.
§ 542. Action on the Heart.—The earlier experimenters on the influence of digitalis on the heart were Stannius and Traube. Stannius[569] experimented on cats, and found strong irregularity, and, lastly, cessation in diastole, in which state it responded no longer to stimuli. Rabbits and birds—especially those birds which lived on plants—were not so susceptible, nor were frogs.
[569] Arch. f. Physiol.
Traube[570] made his researches on dogs, using an extract, and administering doses which corresponded to from ·5 to 4·0 grms. He divided the symptoms witnessed into four stages:—
[570] Ann. d. Charité-Krankenhauses, vol. ii. p. 785.
1st Stage.—The pulse frequently diminishes, while the pressure of the blood rises.
2nd Stage.—Not seen when large doses are employed; pulse frequency, as well as blood pressure, abnormally low.
3rd Stage.—Pressure low, pulse beats above the normal frequency.
The slowing of the heart[571] is attributed to the stimulus of the inhibitory nerves, but the later condition of frequency to their paralysis. After the section of the vagi the slow pulse frequently remains, and this is explained by the inhibitory action of the cardiac centre. The vagus, in point of time, is paralysed earlier than the muscular substance of the heart.
[571] Slowing of the pulse was mentioned first by Withering (An Account of the Foxglove, Lond., 1785). Beddoes afterwards observed that digitalis increased the force of the circulation, the slowing of the pulse not being always observed; according to Ackermann, if the inhibitory apparatus is affected by atropine, or if the patient is under deep narcosis, the slowing is absent.
The increased blood pressure Traube attributed to increased energy of the heart’s contraction, through the motor centre being stimulated later; the commencing paralysis explains the abnormally low pressure.
There is, however, also an influence on vaso-motor nerves. What Dr. Johnson has described as the “stop-cock” action of the small arteries comes into play, the small arteries contract and attempt, as it were, to limit the supply of poisoned blood. Ackermann,[572] indeed, witnessed this phenomenon in a rabbit’s mesentery, distinctly seeing the arteries contract, and the blood pressure rise after section of the spinal cord. This observation, therefore, of Ackermann’s (together with experiments of Böhm[573] and L. Brunton[574]) somewhat modifies Traube’s explanation, and the views generally accepted respecting the cause of the increased blood pressure may be stated thus:—The pressure is due to prolongation of the systolic stroke of the cardiac pump, and to the “stop-cock” action of the arteries; in other words, there is an increase of force from behind (vis a tergo), and an increased resistance in front (vis a fronte).
[572] Deutsch. Arch. f. klin. Med., vol. xix. p. 125.
[573] Archiv f. d. Ges. Phys., vol. v. p. 153.
[574] On Digitalis, with Some Observations on the Urine, Lond., 1868.
§ 543. Action of the Digitalins on the Muco-Intestinal Tract and other Organs.—In addition to that on the heart, there are other actions of the digitalins; for example, by whatever channel the poison is introduced, vomiting has been observed. Even in frogs this, in a rudimentary manner, occurs. The diuretic action which has been noticed in man is wanting in animals, nor has a lessened diminution of urea been confirmed.
Ackermann found the temperature during the period of increased blood pressure raised superficially, but lowered internally. According to Boeck[575] there is no increase in the decomposition of the albuminoids.
[575] Intoxication, p. 404.
§ 544. The Action of Digitalin on the Common Blow-fly.—The author has studied the effects of digitalin, made up into a thin paste with water, and applied to the head of the common blow-fly. There are at once great signs of irritation, the sucker is extruded to its full length, and the fly works its fore feet, attempting to brush or remove the irritating agent. The next symptom is a difficulty in walking up a perpendicular glass surface. This difficulty increases, but it is distinctly observed that weakness and paralysis occur in the legs before they are seen in the wings. Within an hour the wings become paralysed also, and the fly, if jerked from its support, falls like a stone. The insect becomes dull and motionless, and ultimately dies in from ten to twenty-four hours. A dose, in itself insufficient to destroy life, does so on repetition at intervals of a couple of hours. The observation is not without interest, inasmuch as it shows that the digitalins are toxic substances to the muscular substance of even those life-forms which do not possess a heart.
§ 545. Action of the Digitalins on the Frog’s Heart.—The general action of the digitalins is best studied on the heart of the frog. Drs. Fagge and Stevenson have shown[576] that, under the influence of digitalin, there is a peculiar form of irregularity in the beats of the heart of the frog; the ventricle ultimately stops in the white contracted state, the voluntary power being retained for fifteen to twenty minutes afterwards; in very large doses there is, however, at once paralysis. Lauder Brunton[577] considers the action on the heart to essentially consist in the prolongation of the systole.
[576] Guy’s Hospl. Reports, 3rd ver., vol. xii. p. 37.
[577] On Digitalis, with Some Observations on the Urine, Lond., 1868.
Atropine or curare have no influence on the heart thus poisoned. If the animal under the influence of digitalin be treated with muscarine, it stops in diastole instead of systole. On the other hand, the heart poisoned by muscarine is relieved by digitalin, and a similar influence appears to be exercised by atropine. The systolic stillness of the heart is also removed by substances which paralyse the heart, as delphinin, saponin, and apomorphin.
Large doses of digitalin, thrown suddenly on the circulation by intravenous injection, cause convulsions and sudden death, from quick palsy of the heart. With frogs under these circumstances there are no convulsions, but a reflex depression, which, according to Weil[578] and Meihuizen,[579] disappears on decapitation. The central cerebral symptoms are without doubt partly due to the disturbance of the circulation, and there is good ground for attributing them also to a toxic action on the nervous substance. The arteries are affected as well as the heart, and are reduced in calibre; the blood pressure is also increased.[580] This is essentially due to the firm, strong contraction of the heart, and also to the “stop-cock” action of the small arteries.[581]
[578] Archiv f. Anat. u. Physiol., 1871, p. 282.
[579] Archiv f. d. Ges. Physiol., vol. vii. p. 201.
[580] The following is a brief summary of observations on the blood pressure; four stages may be noticed—(1) Rise of normal blood pressure, not necessarily accompanied with a diminution of pulse frequency; (2) continuation of heightened blood pressure, the pulse being raised beyond the normal rate; (3) continued high pressure, with great irregularity of the heart and intermittent pulse; (4) quick depression of pressure, sudden stopping of the heart, and death.
[581] According to Boehm (Arch. f. d. Ges. Physiol., Bd. v. S. 189) and to Williams (Arch. f. exper. Pathol., Bd. xiii. S. 2), the rise of pressure is due entirely to the heart, and not to the contractions of the small arteries; but I fail to see how the small arteries can contract, and yet not heighten the pressure.
§ 546. Post-mortem Appearances.—In the case of the recruit poisoned by digitalis leaf (p. 425), the blood was found dark and fluid; the right ventricle and auricle of the heart were filled with blood, the left empty; the brain and its membranes were anæmic; the stomach and mucous membrane of the intestines were in parts ecchymosed, and there were patches of injection. In the case of the widow De Pauw, poisoned with digitalin by the homœopath (Conty de la Pommerais), the only abnormality discovered was a few hyperæmic points in the mucous membrane of the stomach and small intestines. It is then certain that although more or less redness of the lining membrane of the intestine track may be present, yet, on the other hand, the active principle of the digitalis may destroy life, and leave no appreciable sign.
§ 547. Separation of the Digitalins from Animal Tissues, &c.—It is best to make an alcoholic extract after the method of Stas, the alcohol being feebly acidulated by acetic acid, and all operations being carried on at a temperature below 60°. The alcoholic extract is dissolved in water feebly acidulated by acetic acid, and shaken up, first with petroleum ether to remove impurities (the ether will not dissolve any of the digitalins), then with benzene, and, lastly, with chloroform. The benzene dissolves digitalein, and the chloroform, digitalin and digitoxin. On allowing these solvents to evaporate spontaneously, residues are obtained which will give the reactions already detailed. Neither the bromine nor any other chemical test is sufficient to identify the digitalins; it is absolutely necessary to have resource to physiological experiment. The method used by Tardieu in the classical Pommerais case may serve as a model, more especially the experiments on frogs. Three frogs were properly secured, the hearts exposed, and the beats counted. The number of beats was found to be fairly equal. Frog No. 1 was placed under such conditions that the heart was constantly moist. Frog No. 2 was poisoned by injecting into the pleura 6 drops of a solution in which 10 mgrms. of digitalin were dissolved in 5 c.c. of water. The third frog was poisoned by a solution of the suspected extract. The number of beats per minute were now counted at definite intervals of time as follows:—
TABLE SHOWING THE ACTION OF DIGITALIN ON THE FROG’S HEART.
| Frog No. 1. Unpoisoned. |
Frog No. 2. Poisoned by a known quantity of digitalin. |
Frog No. 3. Poisoned by the suspected extract. |
|||||
|---|---|---|---|---|---|---|---|
| No. of beats per minute. |
No. of beats per minute. |
No. of beats per minute. |
|||||
| After | 6 | minutes, | 42 | 20 | 26 | ||
| „ | 10 | „ | 40 | 16 | irregular. | 24 | irregular. |
| „ | 20 | „ | 40 | 15 | 20 | irre„ | |
| „ | 28 | „ | 38 | 0 | 12 | very irregular. | |
| „ | 31 | „ | 36 | 0 | 0 | ||
In operating in this way—which is strictly comparative, and, with care, has few sources of error—if the heart of the frog poisoned with the unknown extract behaves in the number and irregularity of its contractions similarly to that of the digitalin-poisoned heart, it is a fair inference that, at all events, a “heart-poison” has been separated; but it is, of course, open to question whether this is a digitalin or one of the numerous groups of glucosides acting in the same way. If sufficient quantity has been separated, chemical reactions, especially the bromine test (Grandeau’s test), may decide, but with the larger number (yearly increasing) of substances acting similarly on the heart, great caution in giving an opinion will be necessary.
§ 548. Several members of these glucosides have been studied by Schmiedeberg,[582] and his convenient divisions will be followed here:—
[582] Beiträge zur Kentniss der pharmakol. Gruppe des Digitalins.
Antiarin (C14H20O5).—Antiarin is an arrow poison obtained from the milky juice of the Antiaris toxicaria growing in Java. Antiarin is obtained in crystals, by first treating the inspissated milky juice with petroleum ether to remove fatty and other matters, and then dissolving the active principle out with absolute alcohol. The alcoholic extract is taken up with water, precipitated with lead acetate, filtered, and from the filtrate antiarin obtained by freeing the solution from lead, and then evaporating. De Vry and Ludwig obtained about 4 per cent. from the juice. Antiarin is crystalline, the crystals containing 2 atoms of water. Its melting-point is given as 220·6°; the crystals are soluble in water (254 parts cold, 27·4 parts boiling), they are not soluble in benzene, and with difficulty in ether; 1 part of antiarin requiring 2792 parts of ether.
The watery solution is not precipitated by metallic salts. On warming with dilute mineral acids, antiarin splits up into a resin and sugar. Concentrated sulphuric acid gives with antiarin a yellow-brown solution, hydrochloric and nitric acids strike no distinctive colours.
§ 549. Effects.—Antiarin is essentially a muscular and a heart poison. When given in a sufficient dose, it kills a frog in from half an hour to an hour. Its most marked effect is on the cardiac muscle, the heart beats more and more slowly, and at last stops, the ventricle being firmly contracted. As with digitalin, there is a very marked prolongation of the systole, and as with digitalin, after the beats have ceased, a forcible dilatation of the ventricle will restore them (Schmiedeberg). It is doubtful whether by physiological experiment antiarin could be differentiated from digitalin.
§ 550. Separation of Antiarin.—In any case of poisoning by antiarin, it would be best to extract with alcohol, evaporate, dissolve the alcoholic extract in water, precipitate with lead acetate, filter, free the filtrate from lead, and then, after alkalising with ammonia, shake the filtrate successively with petroleum ether, benzene, and a small quantity of ether in the manner recommended at page 247, et seq. The liquid, now freed from all fatty, resinous, and alkaloidal bodies, is neutralised and evaporated to dryness in a vacuum, and the dry residue taken up with absolute alcohol, filtered, the alcohol evaporated at a very low temperature, and finally the extract dissolved in a small quantity of water, and submitted to physiological tests.
§ 551. The Active Principles of the Hellebores.—The Christmas rose (Helleborus niger), as well as H. viridis, H. fœtidus, and, in short, all the species of hellebore, are poisonous, and if the root is treated with alcohol, from the alcoholic extract may be separated two glucosides, helleborin and helleborein.
Helleborin is in the form of white, glittering needles, which, if placed on the tongue, are almost tasteless, but if dissolved in alcohol, and then tasted, give a burning, numbing sensation. By boiling with zinc chloride, helleborin splits up into sugar and a resin—helleboresin. Concentrated sulphuric acid dissolves the crystals with the production of a beautiful red colour; on standing, the solution after a while becomes colourless, and a white powder separates.
Helleborein forms colourless crystals, mostly consisting of fine needles; they have a bitter taste, excite sneezing, and are very hygroscopic. The crystals easily dissolve in water and dilute alcohol, but are with difficulty soluble in absolute alcohol, and not soluble in ether. They dissolve in fatty oils. Helleborein splits by the action of mineral acids into sugar and amorphous helleboretin.
Helleboretin is in the moist condition of a beautiful violet-blue colour, becoming, when dried at 100°, dirty green. Concentrated sulphuric acid dissolves it with the production of a brown-yellow colour, which on standing passes into violet and then into brown.
Marmé separated from H. fœtidus, in addition, a white, intensely odorous substance, but too small in quantity to thoroughly investigate its properties.
§ 552. There is little doubt that hellebore owes its properties to the glucosides just described. There are several instances of poisoning by hellebore root,[583] and by the pharmaceutical preparations, but none of poisoning by the pure active principles. Morgagni mentions a case in which 2 grms. (nearly 31 grains) of the watery extract of H. Niger caused death within eight hours; and Ferrari saw, after the use of the wine in which the root had been boiled, two persons poisoned with a like result. A more recent case was recorded by Felletar, in 1875, in which a person died from an infusion of hellebore; there was, however, old standing heart-disease, so that there may be a doubt as to the real cause of death in this instance. Schauenstein mentions a case in which the roots of hellebore were accidentally used in soup, but the bitter taste prevented any quantity being eaten. The physiological action, especially of helleborein, is that of an intense heart poison, and the symptoms produced by the hellebores are so strikingly like those of the digitalins that it might be difficult to distinguish clinically between them. In any case of poisoning, the active principle must be separated in the form of an alcoholic extract, and identified as a heart poison by physiological experiment.
[583] There used to be a tincture officinal in our pharmacopœia; the root of H. viridis is officinal in the German pharmacopœia, maximum single dose, ·3 grm.; maximum total quantity in twenty-four hours, 1·2 grm. The tincture is also officinal on the Continent.
§ 553. Euonymin is found in a resin obtained from the Euonymus atropurpureus; it is crystalline, crystallising in colourless, cauliflower-like masses consisting of groups of stellate needles, which are soluble in water, but with difficulty in alcohol. It is a glucoside, and a powerful heart poison, 1 mgrm. causing the heart of a frog to cease in diastole.[584]
[584] Schmiedeberg, op. cit., from unpublished researches of Professor H. Meyer, Dorpat.
§ 554. Thevetin (C54H48O2).—A glucoside which has been separated from the Thevetia nereifolia, and perhaps also from the Cerbera Odallam. It is soluble in 124 parts of water at 14°, and is easily soluble in spirit, but not in ether. It is coloured by sulphuric acid red-brown, passing into cherry-red, and then, in a few hours, into violet. On boiling with diluted acids, it splits up into sugar and theveresin. Both thevetin and theveresin are powerful heart poisons.[585]
[585] Husemann, Archiv f. exper. Path. u. Pharmakol., Bd. v., S. 228, 1876.
§ 555. Strophantin is a very poisonous substance which belongs physiologically to this group, but does not seem to be a glucoside. It is soluble in water and in alcohol, less so in ether and chloroform. It is found in the kombé, manganja, inée, or onaje, a West African poison derived from the Strophanthus hispidus of the family of Apocynaceæ. The poison has been investigated by several observers.[586]
Dr. Fraser considers, from his experiments, (1) That strophantin acts primarily on the heart, producing, as an end result, heart paralysis, with permanence of the ventricular systole. (2) He found the pulmonary respiration to continue in cold-blooded animals many minutes after the heart was paralysed. (3) The striped muscles of the body are affected, and twitches occur in them; their tonicity is exaggerated, and finally their functional activity is destroyed. This change is referred to an action on the muscular structure itself, independent of that upon the heart, and also independent of the cerebro-spinal nervous system. (4) The reflex action of the spinal cord is suspended after the heart is paralysed, but the motor conductivity of the spinal cord and of the nerve trunks continue after the striped muscles of the body are paralysed. (5) The lymph-hearts of the frog continue to contract for many minutes after the blood-heart has been paralysed.
§ 556. Apocynin.—In the root of Apocynum cannabinum a non-crystallisable substance, soluble in alcohol and ether, but not soluble easily in water, has been separated and found to have a physiological activity similar to that of the digitalins.[587]
[587] Hardy et Callois, “Sur la matière active du Strophanthus Hispidus ou Inée,” Gaz. Med. de Paris; Pelikan, Compt. Rend., t. 60, p. 1209, 1815; Sharpey, Proc. Roy. Soc., May, 1865; Fagge and Stevenson, Pharm. Journ., p. 11, 1865-66; Fraser, Journ. of Anatom. and Phys., also Proc. of Roy. Soc. of Edin.; Poillo and Carville, Arch. de Physiol. Norm. et Pathol., 1872; G. Valentin, Zeitschr. et. Biologie., x. 133, 1874.
§ 557. Scillain, or Scillitin, a glucoside which has been separated from the bulbs of the common squill. It is insoluble or nearly so in water, but easily dissolves in alcohol. It is little soluble in ether. It acts upon the heart, and is poisonous.
Adonidin, a very similar substance, has been separated from the root of the Adonis vernalis (Nat. Ord. Ranunculaceæ), to which the name of adonidin has been given.[588] It is an amorphous, colourless substance, without odour; soluble in alcohol, but with difficulty soluble in ether and water. It is precipitated by tannin, and on saponification by mineral acids, splits up into sugar and a substance soluble in ether. The effects on animals are identical with those of digitalin. The root has been used recently in medicine, and found to slow the heart and increase the urinary secretion; in this also it is like digitalis.
[588] Cervello, Archiv für exp. Path. Pharm., 1882, p. 338.
§ 558. Oleandrin.—Oleander leaves contain two chemically-different, nitrogen-free substances. The one is probably identical with digitalein; but as this is not certain, Schmiedeberg proposes to call it provisionally neriin. The other active substance is essentially the same as the oleandrin of Lukomske[589] and Betelli.[590] Oleandrin has basic properties, and is separated in the form of an amorphous mass, soluble in alcohol, ether, and chloroform, and slightly soluble in water. Schmiedeberg obtained a third product from African leaves, which he calls nerianthin. This, on treatment with sulphuric acid and bromine, gives a beautiful colour peculiar to oleander leaves. It is very similar in physiological and chemical properties to digitalin, and is probably derived by decomposition from one of the principles already described. There is also a product similar to digitaliresin.
[589] Repert. de Chimie de Wurtz et Bareswill, t. iii. p. 77, 1861.
[590] Bull. Med. di Bologna, t. xix. p. 321, 1865.
The active principles of the oleander are separated by digestion of the leaves with alcohol of 50 per cent., and precipitating the alcoholic extract with lead acetate and ammonia. The first precipitate is yellow, and is probably composed of a tannin-like substance; the next precipitate is white, consisting of the lead compound of neriin. The precipitates are filtered off, and the filtrate concentrated; nerianthin, after a while, separates in light flocks, and the filtrate from this contains some of the other products.
§ 559. Neriin or Oleander Digitalin.—Neriin is, in the presence of much free mineral acid, precipitated by potass-bismuth iodide, a reaction first pointed out by Marmé,[591] as useful in the isolation of the helleborins; or it may be precipitated by tannin, and then the precipitate decomposed by dissolving in alcohol, and evaporating it to dryness with zinc oxide on the water-bath. It is next extracted by absolute alcohol, and precipitated by the addition of much ether. The further purification consists of resolution in alcohol, and fractional precipitation by ether. If, however, the potass-bismuth iodide process is used, the liquid must be acidified strongly with sulphuric acid, and the precipitate washed with diluted sulphuric acid. The precipitate may be decomposed by baryta, filtered, and the filtrate freed from baryta by carbon dioxide; the filtrate from this contains neriin with baric iodide; it is therefore treated with silver sulphate, then again with baryta, next with carbon dioxide, and also with SH2 to get rid of the last trace of silver.
The filtrate will also contain some oleandrin which, by evaporating slowly in a vacuum, separates gradually in the form of a clear, resinous mass. It can be filtered off, and the neriin then may be precipitated pure by fractional precipitation. Its physiological action is the same as that of digitalein.