[412] Sitzungsber. d. Wien. Akadem., lvi. pp. 2, 89, 1867; Arch. f. Anat. u. Physiol., Hft. 1, p. 112, 1869.
[413] F. W. Müller, Das Thebaine, eine Monographie, Diss., Marburg 1868.
The fatal dose for a man is not known; ·5 grm., or about 8 grains, would probably be a poisonous quantity.
§ 376. Cryptopine (C21H23NO5) was discovered by T. & H. Smith in 1867.[414] It is only contained in very minute traces in opium—something like ·003 per cent. It is a crystalline substance, the crystals being colourless, six-sided prisms, without odour, but with a bitter taste, causing an after-sensation like peppermint. The crystals melt at 217°, and congeal in a crystalline form again at 171°; at high temperatures they are decomposed with evolution of ammoniacal vapour. Cryptopine is insoluble, or almost so, in ether, water, and oil of turpentine; it is soluble in acetone, benzene, and chloroform; the latter is the best solvent, or hot alcohol; it is insoluble in aqueous ammonia and in solutions of the caustic alkaloids. Cryptopine is strongly basic, neutralising fully mineral acids. Concentrated sulphuric acid colours cryptopine pure blue, the tint gradually fading from absorption of water from the atmosphere. On a crystal of potassic nitrate being added, the colour changes into a permanent green. With ferric chloride cryptopine gives no colour—thus distinguishing it from morphine. The physiological properties of cryptopine have been investigated by Dr. Harley;[415] it has a narcotic action, about double as strong as narceine, and four times weaker than morphine. Munk and Sippell[416] found that it gave rise in animals to paralysis of the limbs, and occasionally asphyxic convulsions before death.
[414] Pharm. Journ. Trans. [2], viii. pp. 495 and 716.
[415] The Old Vegetable Neurotics.
[416] Munk, Versuche über die Wirkung des Cryptopins, Berlin, 1873. Sippell, Beiträge zur Kentniss des Cryptopins, Marburg, 1874.
§ 377. Rhœadine (C21H21NO6).—Rhœadine was separated from Papaver rhœas by Hesse, and has also been found in Papaver somniferum and in opium. Rhœadine is in the form of small anhydrous tasteless prisms, melting at 230° and partly subliming. In a vacuum sublimation is almost complete, and at a much lower temperature. It is a very insoluble substance, and is scarcely dissolved, when crystalline, by water, alcohol, ether, chloroform, benzene, and solutions of the fixed or volatile alkalies. When in an amorphous state it is rather soluble in ether, and may be dissolved out of any substance by treating with dilute acetic acid, and neutralising by ammonia, and shaking up with ether before the precipitate becomes crystalline. Rhœadine is easily recognised by its striking a red colour with hydrochloric acid. Either spontaneously or on gentle warming, the colour is produced—one part of rhœadine will colour in this way 10,000 parts of acid water blue or purple-red, 200,000 rose-red, and 800,000 pale red. The reaction depends on a splitting up of the rhœadine into a colourless substance, rhœadin, and a red colouring-matter. Rhœadine is not poisonous.
§ 378. Pseudomorphine (C17H19NO4).—Pseudomorphine was discovered by Pelletier and Thiboumery in 1835. As precipitated by ammonia out of the hot solution, pseudomorphine falls as a white crystalline precipitate; but if the solution is cold, the precipitate is gelatinous. It possesses no taste, and has no action on vegetable colours. On heating, it decomposes and then melts. It dissolves easily in caustic alkalies and in milk of lime, but is insoluble in all the ordinary alcoholic and ethereal solvents, as well as in diluted sulphuric acid. The most soluble salt is the hydrochlorate (C17H19NO4HCl + H2O), and that requires 70 parts of water at 20° for solution. Various salts, such as the sulphate, oxalate, &c., may be prepared from the hydrochlorate by double decomposition. Concentrated sulphuric acid dissolves pseudomorphine gradually, with the production of an olive-green colour.
§ 379. Opianine (C66H72N4O21).—Opianine crystallises in colourless, glittering ortho-rhombic needles. Ammonia precipitates it from its solution in hydrochloric acid as a fine white powder. It is without odour, and has a bitter taste. It is a strong base, and is soluble in cold, but slightly soluble in boiling water. It is also but little soluble in boiling alcohol.
An alcoholic solution of the alkaloid gives a voluminous precipitate with mercuric chloride; after standing a little time, the precipitate becomes crystalline, the crystals being in the shape of fine needles. They have the following composition—C66H72N4O21, 2HCl, 2HgCl—and are with difficulty soluble in water or alcohol.
Opianine, administered to cats in doses of ·145 grm., produces complex symptoms—e.g., dilated pupils, foaming at the mouth, uncertain gait, paralysis of the hinder extremities, and stupor—but the alkaloid is rare, and few experiments have been made with it.
§ 380. Apomorphine (C17H19NO3).—Apomorphine is a derivative of morphine, and is readily prepared by saponifying morphine by heating it with dilute hydrochloric acid in sealed tubes. The result is apomorphine hydrochloride, the morphine losing one molecule of water, according to the equation C17H19NO3 = C17H17NO2 + H2O.
To extract apomorphine, the bases are precipitated by sodic bicarbonate, and the precipitate extracted by ether or chloroform, either of which solvents leaves morphine undissolved. The apomorphine is again converted into hydrochloride, and once more precipitated by sodic bicarbonate, and is lastly obtained as a snow-white substance, rapidly becoming green on exposure to the air. The mass dissolves with a beautiful green colour in water, and also in alcohol, whilst it colours ether purple-red, and chloroform violet.
A test for apomorphine is the following:—The chloride is dissolved in a little acetic acid and shaken with a crystal of potassic iodate (KIO3); this immediately turns red from liberated iodine on shaking it up with a little chloroform; on standing, the chloroform sinks to the bottom, and is coloured by the alkaloid a beautiful blue colour; on now carefully pouring a little CS2 on the surface of the liquid at the point of junction it is coloured amethyst owing to dissolved iodine, and apocodeine gives a similar reaction.
Apomorphine is the purest and most active emetic known: whether injected beneath the skin or taken by the mouth, the effect is the same—there is considerable depression, faintness, and then vomiting. The dose for an adult is about 6 mgrms. (·092 grain) subcutaneously administered.
§ 381. The reactions of some of the rarer alkaloids of opium with sulphuric acid and ferric chloride are as follows: none of them have at present any toxicological importance:—
TABLE SHOWING SOME OF THE REACTIONS OF THE RARER ALKALOIDS OF OPIUM.
| Alkaloid. | Formula. | Reaction with Warm Sulphuric Acid. |
Reaction with Ferric Chloride. |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Codamine, | C20H25NO4 | - | Dirty red-violet colour, turning dark violet on the addition of HNO3. | - | Dark green. | ||||
| Landamine, | C20H25NO4 | ||||||||
| Landanosine, | C20H27NO4 | - | Dirty green to brownish-green. | - | No colour. | ||||
| Protapine, | C20H19NO5 | ||||||||
| Lanthopine, | C23H25NO4 | Dark brown or black. | No colour. | ||||||
| Hydrocotarnine, | C12H15NO3 | Dirty red-violet; not changed by trace of HNO3. | No colour. | ||||||
§ 382. Tritopine (C42H54N2O7).—This is a rare alkaloid that has been found in small quantities in opium. It is crystalline, separating in transparent prisms. Melting-point 182°. It is soluble in alcohol and chloroform, and slightly soluble in ether.[417]
[417] E. Kander, Arch. Pharm., 228, pp. 419-431.
§ 383. Meconin (Opianyl) (C10H10O4) is in the form of white glittering needles, which melt under water at 77° and in air at 90°, again coagulating at 75°. It may be sublimed in beautiful crystals. It is soluble in 22 parts of boiling, and 700 of cold water; dissolves easily in alcohol, ether, acetic acid, and ethereal oil, and is not precipitated by acetate of lead. Its solution in concentrated sulphuric acid becomes, on warming, purple, and gives, on the addition of water, a brown precipitate. Meconin may be prepared by treating narcotine with nitric acid. Meconin, in large doses, is a feeble narcotic; 1·25 grm. (20 grains) has been given to man without result.
§ 384. Meconic Acid (C7H4O7) crystallises in white shining scales or small rhombic prisms, with three atoms of water (C7H4O7 + 3H2O), but at 100° this is lost, and it becomes an opaque white mass. It reddens litmus, and has a sourish taste. It is soluble in 115 parts of cold, but dissolves in 4 parts of boiling water; it dissolves easily in alcohol, less so in ether. It forms well-marked salts; the barium and calcium salt crystallise with one atom of water, the former having the composition BaH4(C7HO7)2; the latter, if ammonium meconate is precipitated by calcium chloride, CaH4(C7HO7)2; but if calcium chloride is added to the acid itself, the salt has the composition C7H2CaO7 + H2O. If meconic acid is gently heated, it decomposes into carbon dioxide and comenic acid (C6H4O5). If the heat is stronger, pyromeconic acid (C5H4O3)—carbon dioxide, water, acetic acid, and benzole are formed. Pyromeconic acid is readily sublimed in large transparent tables. Chloride of iron, and soluble iron salts generally, give with meconic acid (even in great dilution) a lively red colour, which is not altered by heat, nor by the addition of HCl nor by that of gold chloride. Sugar of lead and nitrate of silver each give a white precipitate; and mercurous and mercuric nitrates white and yellow precipitates. In any case where the analyst has found only meconic acid, the question may be raised in court as to whether it is a poison or not. The early experiments of Sertürner,[418] Langer, Vogel, Sömmering, and Grape[419] showed that, in comparatively speaking large doses, it had but little, if any, action on dogs or men. Albers[420] has, however, experimented on frogs, and found that in doses of ·1 to ·2 grm. there is, first, a narcotic action, and later, convulsions and death. According to Schroff,[421] there is a slight narcotic action on man.
[418] Ann. Phys., xxv. 56; xxvii. 183.
[419] De opio et de illis quibus constat partibus, Berol., 1822.
[420] Arch. Path. Anat., xxvi. 248.
[421] Med. Jahresb., 1869.
The most generally accepted view at the present time is that the physiological action of meconic acid is similar to that of lactic acid—viz., large doses cause some depression and feeble narcosis.
In a special research amongst organic fluids for meconic acid, the substances are extracted by alcohol feebly acidulated with nitric acid; on filtration the alcohol, after the addition of a little water, is distilled off, and to the remaining fluid a solution of acetate of lead is added, and the whole filtered. The filtrate will contain any alkaloids, whilst meconic acid, if present, is bound up with the lead on the filter. The meconate of lead may be either washed or digested in strong acetic acid to purify it, suspended in water, and freed from lead by SH2; the filtrate from the lead sulphide may be tested by ferric chloride, or preferably, at once evaporated to dryness, and weighed. After this operation it is identified. If the quantity is so small that it cannot be conveniently weighed, it may be estimated colorimetrically, by having a standard solution of meconic acid, containing 1 mgrm. in every c.c. A few drops of neutral ferric chloride are added in a Nessler cylinder to the liquid under examination; and the tint thus obtained is imitated in the usual way, in another cylinder, by means of ferric chloride, the standard solution, and water. It is also obvious that the weight of the meconic acid may be increased by converting it into the barium salt—100 parts of anhydrous baric meconate, (Ba2C7H2O7), being equivalent to 42·3 of meconic acid (C7H4O7).
[422] To this group also belong some of the opium alkaloids. See “Thebaine,” “Landamine,” “Codeine,” “Hydrocotarnine.”
§ 385. Nux vomica is found in commerce both in the entire state and as a powder. It is the seed of the Strychnos nux vomica, or Koochla tree. The seed is about the size of a shilling, round, flattened, concavo-convex, of a yellowish-grey or light-brown colour, covered with a velvety down of fine, radiating, silky hairs, which are coloured by a solution of iodine beautiful gold-yellow; the texture is tough, leathery, and not easily pulverised; the taste is intensely bitter. The powder is not unlike that of liquorice, and, if met with in the pure state, gives a dark orange-red colour with nitric acid, which is destroyed by chloride of tin; the aqueous infusion gives a precipitate with tincture of galls, is reddened by nitric acid, and gives an olive-green tint with persulphate of iron. The best method, however, of recognising quickly and with certainty that the substance under examination is nux vomica powder, is to extract strychnine from it by the following simple process:—The powder is completely exhausted by boiling alcohol (90 per cent.), the alcoholic extract evaporated to dryness, and then treated with water; the aqueous solution is passed through a wet filter, and concentrated by evaporation to a small bulk. To this liquid a drop or so of a concentrated solution of picric acid is added, and the yellow precipitate of picrates thus obtained is separated, treated with nitric acid, the picric acid removed by ether, and the pure alkaloid precipitated by soda, and shaken out by chloroform.
§ 386. Chemical Composition.—Nux vomica contains at least four distinct principles:—
§ 387. Strychnine (C21H22N2O2) is contained in the bean of S. ignatius, in the bark (false angustura bark) and seeds of the Strychnos nux vomica, in the Strychnos colubrina, L., in the Strychnos tieuté, Lesch, and probably in various other plants of the same genus.
Commercial strychnine is met with either in colourless crystals or as a white powder, the most usual form being that of the alkaloid itself; but the nitrate, sulphate, and acetate are also sold to a small extent.
The microscopical appearance of strychnine, as thrown down by the solution of vapour of ammonia, may be referred to three leading forms—the long rectangular prism, the short hexagonal prism, or the regular octahedron. If obtained from the slow evaporation of an alcoholic solution, it is usually in the form of four-sided pyramids or long prisms; but if obtained by speedy evaporation or rapid cooling, it appears as a white granular powder. If obtained from a benzene solution, the deposit is usually crystalline, but without a constant form, though at times the crystals are extremely distinct, the short six-sided prism prevailing; but triangular plates, dodecahedral, rhomboidal, and pentagonal, may also be met with. An ethereal solution on evaporation assumes dendritic forms, but may contain octahedra and four-sided prisms. A chloroform solution deposits rosettes, veined leaves, stellate dotted needles, circles with broken radii, and branched and reticulated forms of great delicacy and beauty.—Guy.
Strychnine is very insoluble in water, although readily dissolved by acidulated water. According to Wormley’s repeated experiments, one part of strychnine dissolves in 8333 parts of cold water; and, according to Pelletier and Cahours, it dissolves in 6667 parts of cold, and 2500 parts of boiling water. It may be convenient, then, to remember that a gallon of cold water would hardly dissolve more than 10 grains (·142 grm. per litre); the same amount, if boiling, about 30 grains (·426 grm. per litre) of strychnine. The solubility of one part of strychnine in other menstrua is as follows:—Cold alcohol, 0·833 specific gravity, 120, boiling, 10 parts (Wittstein); cold alcohol, 0·936 specific gravity, 240 parts (Merck); cold alcohol, 0·815 specific gravity, 107 parts (Dragendorff); amyl alcohol, 181 parts; benzene, 164; chloroform, 6·9 (Schlimpert), 5 (Pettenkofer); ether, 1250 parts; carbon disulphide, 485 parts; glycerin, 300 parts. Creosote and essential and fixed oils also dissolve strychnine.
Of all the above solvents, it is evident that chloroform is the best for purposes of separation, and next to chloroform, benzene.
If a speck of strychnine be placed in the subliming cell, it will be found to sublime usually in a crystalline form at 169°. A common form at this temperature, according to the writer’s own observations, is minute needles, disposed in lines; but, as Dr. Guy has remarked, the sublimate may consist of drops, of waving patterns, and various other forms; and, further, while the sublimates of morphia are made up of curved lines, those of strychnine consist of lines either straight or slightly curved, with parallel feathery lines at right angles. On continuing the heat, strychnine melts at about 221°, and the lower disc, if removed and examined, is found to have a resinous residue; but it still continues to yield sublimates until reduced to a spot of carbon. The melting-point taken in a tube is 268°.
Strychnine is so powerfully bitter, that one part dissolved in 70,000 of water is distinctly perceptible; it is a strong base, with a marked alkaline reaction, neutralising the strongest acids fully, and precipitating many metallic oxides from their combinations, often with the formation of double salts. Most of the salts of strychnine are crystalline, and all extremely bitter. Strychnine, in the presence of oxygen, combines with SH2 to form a beautiful crystalline compound:—
2C21H22N2O2 + 6H2S + O3 = 2C21H22N2O23H2S2 + 3H2O.
On treatment with an acid this compound yields H2S2.—Schmidt, Ber. Deutsch. Chem. Ges., 8, 1267.
An alcoholic solution of strychnine turns the plane of polarisation to the left, [α]r = -132·08° to 136·78° (Bouchardat); but acid solutions show a much smaller rotatory power.
The salts used in medicine are—the sulphate, officinal only in the French pharmacopœia; the nitrate, officinal in the German, Austrian, Swiss, Norse, and Dutch pharmacopœias; and the acetate, well known in commerce, but not officinal.
The commercial Sulphate (C21H22N2O2H2SO4 + 2H2O) is an acid salt crystallising in needles which lose water at 150°, the neutral sulphate (2C21H22N2O2,H2SO4 + 7H2O) crystallises in four-sided, orthorhombic prisms, and is soluble in about 50 parts of cold water.
The Nitrate (C21H22N2O2,HNO3) crystallises on evaporation from a warm solution of the alkaloid in dilute nitric acid, in silky needles, mostly collected in groups. The solubility of this salt is considerable, one part dissolving in 50 of cold, in 2 of boiling water; its solubility in boiling and cold alcohol is almost the same, taking 60 of the former and 2 of the latter.
The Acetate crystallises in tufts of needles; as stated, it is not officinal in any of the European pharmacopœias.
The chief precipitates or sparingly soluble crystalline compounds of strychnine are—
(1.) The Chromate of Strychnine (C21H22N2O2CrHO2), formed by adding a neutral solution of chromate of potash to a solution of a strychnine salt, crystallises out of hot water in beautiful, very insoluble, orange-yellow needles, mixed with plates of various size and thickness. The salt is of great practical use to the analyst; for by its aid strychnine may be separated from a variety of substances, and in part from brucine—the colour tests being either applied direct to the strychnine chromate, or the chromate decomposed by ammonia, and the strychnine recovered from the alkaline liquid by chloroform.
(2.) Sulphocyanide of Strychnine (C21H22N2O2CNHS) is a thick, white precipitate, produced by the addition of a solution of potassic sulphocyanide to that of a strychnine salt; on warming it dissolves, but on cooling reappears in the form of long silky needles.
(3.) Double Salts.—The platinum compound obtained by adding a solution of platinic chloride to one of strychnine chloride has the composition C21H22N2O2HClPtCl2, and crystallises out of weak boiling alcohol (in which it is somewhat soluble) in gold-like scales. The similar palladium compound (C21H22N2O2HCl,PdCl) is in dark brown needles, and the gold compound (C21H22N2O2HClAuCl3) in orange-coloured needles.
(4.) Strychnine Trichloride.—The action of chlorine on strychnine—by which chlorine is substituted for a portion of the hydrogen—has been proposed as a test. The alkaloid is dissolved in very dilute HCl, so as to be only just acid; on now passing through chlorine gas, a white insoluble precipitate is formed, which may be recrystallised from ether; it has probably the composition C21H19Cl3N2O2, and is extremely insoluble in water.
(5.) The Iodide of Strychnine (C21H22N2O2HI3) is obtained by the action of iodine solution on strychnine sulphate; on solution of the precipitate in alcohol, and evaporation, it forms violet-coloured crystals, very similar to those of potassic permanganate.
§ 388. Pharmaceutical and other Preparations of Nux Vomica and Strychnine, with Suggestions for their Valuation.
An aqueous extract of nux vomica, officinal in the German pharmacopœia, appears to contain principally brucine, with a small percentage of strychnine; the proportion of brucine to strychnine being about four-fifths to one-fifth. Blossfield found in a sample 4·3 per cent. of total alkaloid, and two samples examined by Grundmann consisted (No. 1) of strychnine, 0·6 per cent.; brucine, 2·58 per cent.—total, 3·18 per cent.; (No. 2) strychnine, 0·68 per cent.; brucine, 2·62 per cent.—total, 3·3 per cent. A sample examined by Dragendorff yielded—strychnine, 0·8 per cent.; brucine, 3·2 per cent.—total, 4 per cent. The maximum medicinal dose is put at ·6 grm. (91⁄14 grains).
The spirituous extract of nux vomica, officinal in the British and all the Continental pharmacopœias, differs from the aqueous in containing a much larger proportion of alkaloids, viz., about 15 per cent., and about half the total quantity being strychnine. The medicinal dose is 21·6-64·8 mgrms. (1⁄3 grain to a grain).
There is also an extract of St. Ignatius bean which is used in the United States; nearly the whole of its alkaloid may be referred to strychnine.
The tincture of nux vomica, made according to the British Pharmacopœia, contains in 1 fl. oz. 1 grain of alkaloids, or 0·21 part by weight in 100 by volume, but the strength of commercial samples often varies. Lieth found in one sample 0·122 per cent. of strychnine and 0·09 per cent. brucine; and two samples examined by Wissel consisted respectively of 0·353 per cent. and 0·346 per cent. of total alkaloids. Dragendorff found in two samples ·2624 per cent. and ·244 per cent. of total alkaloids, about half of which was strychnine.
Analysis.—Either of the extracts may be treated for a few hours on the water-bath, with water acidulated by sulphuric acid, filtered, the residue well washed, the acid liquid shaken up with benzene to separate impurities, and, on removal of the benzene, alkalised with ammonia, and shaken up two or three times with chloroform; the chloroform is then evaporated in a tared vessel, and the total alkaloids weighed. The alkaloids can then be either (a) treated with 11 per cent. of nitric acid on the water-bath until all the brucine is destroyed, and then (the liquid being neutralised) precipitated by potassic chromate; or (b) the alkaloids may be converted into picrates. Picrate of strychnine is very insoluble in water, 1 part requiring no less than 10,000 of water.[423] The tincture is analysed on precisely similar principles, the spirit being got rid of by distillation, and the residue treated by acidified water, &c.
[423] Dolzler, Arch. Pharm. [3], xxiv. 105-109.
The nux vomica powder itself may be valued as follows:—15 to 20 grms., pulverised as finely as possible, are treated three times with 150 to 300 c.c. of water, acidified with sulphuric acid, well boiled, and, after each boiling, filtered and thoroughly pressed. The last exhaustion must be destitute of all bitter taste. The united filtrates are then evaporated to the consistence of a thick syrup, which is treated with sufficient burnt magnesia to neutralise the acid. The extract is now thoroughly exhausted with boiling alcohol of 90 per cent.; the alcoholic extract, in its turn, is evaporated nearly to dryness, and treated with acidulated water; this acid solution is freed from impurities by shaking up with benzene, and lastly alkalised with ammonia, and the alkaloids extracted by shaking up with successive portions of chloroform. The chloroformic extract equals the total alkaloids, which may be separated in the usual way.
In four samples of nux vomica examined by Dragendorff, the total alkaloids ranged from 2·33 to 2·42 per cent. Grate found in two samples 2·88 per cent. and 2·86 per cent. respectively; while Karing from one sample separated only 1·65 per cent. The strychnine and brucine are in about equal proportions, Dragendorff[424] finding 1·187 per cent. strychnine and 1·145 per cent. brucine.[425]
[424] Dragendorff, Die chemische Werthbestimmung einiger starkwirkenden Droguen, St. Petersburg, 1874.
[425] These details are very necessary, as bearing on the question of the fatal dose of nux vomica, which Taylor tells us (Med. Jurisprud., i. 409) was of some importance in Reg. v. Wren, in which 47 grains were attempted to be given in milk. The fatal dose of nux vomica must be ruled by its alkaloidal content, which may be so low as 1 per cent., and as high as nearly 3 per cent. 30 grains have proved fatal (Taylor); if the powder in this instance was of the ordinary strength, the person died from less than a grain (·0648 grm.) of the united alkaloids.
The vermin-killers in use in this country are those of Miller, Battle, Butler, Clift, Craven, Floyd, Gibson, Hunter, Stenier, and Thurston. Ten samples from these various makers were examined recently by Mr. Allen (Pharm. Journal, vol. xii., 1889), and the results of the analyses are embodied in the following table:—
| Name or Mark. |
Weight of Powder in Grains. |
Price. | Strychnine. | Nature of Starch. |
Colouring Matter. |
|
|---|---|---|---|---|---|---|
| Weight in Grains. |
Per- centage. |
|||||
| 1 | 5·6 | 3d. | 0·61 | 10·9 | Wheat | ? |
| 2 | 11·8 | 3d. | 0·80 | 6·7 | Wheat | Ultramarine. |
| 3 | 13·1 | 3d. | 1·12 | 8·7 | Rice | Ultramarine. |
| 4 | 11·6 | 3d. | 1·28 | 11·1 | Rice | Ultramarine. |
| 5 | 13·1 | 3d. | 1·70 | 13·0 | Rice | Ultramarine. |
| 6 | 21·5 | 6d. | 2·42 | 11·2 | Wheat | Prussian blue. |
| 7 | 49·2 | 3d. | 2·85 | 5·8 | Wheat | Soot. |
| 8 | 30·5 | 3d. | 3·45 | 11·3 | Wheat | Prussian blue. |
| 9 | 16·6 | 3d. | 3·81 | 19·4 | Rice | Carmine. |
| 10 | 10·0 | 3d. | 4·18 | 41·8 | Rice | Ultramarine. |
§ 389. Statistics.—In England, during the ten years 1883-92, out of 6666 total deaths from poison, strychnine, nux vomica, and vermin-killer account for 325. Out of these deaths, 118 were ascribed to “vermin-killer.” “Vermin-killer” may be presumed to include not only strychnine mixtures, but also phosphorus and arsenic pastes and powders, so that there are no means of ascertaining the number of strychnine cases comprised under this heading. Taking the deaths actually registered as due to strychnine or nux vomica, they are about 4·7 per cent. of the deaths from all sorts of poison. Of these deaths, 268, or 82·4 per cent., were suicidal, 8 were homicidal, and 49 only were accidental.
Schauenstein has collected from literature 130 cases of poisoning by strychnine, but most of these occurred during the last twenty-five years; 62 of the 130, or about one-half, were fatal, and 15 were homicidal. It has been stated that strychnine is so very unsuitable for the purpose of criminal poisoning as to render it unlikely to be often used. Facts, however, do not bear out this view; for, allowing its intensely bitter taste, yet it must be remembered that bitter liquids, such as bitter ale, are in daily use, and a person accustomed to drink any liquid rapidly might readily imbibe sufficient of a toxic liquid to produce death before he was warned by its bitterness. It is, indeed, capable of demonstration, that taste is more vivid after a substance has been taken than just in the act of swallowing, for the function of taste is not a rapid process, and requires a very appreciable interval of time.
The series of murders by Thomas Neill, or, more correctly, Thomas Neill Cream, is an example of the use of strychnine for the purposes of murder. Thomas Neill Cream was convicted, October 21, 1892, for the murder of Matilda Clover on October 20, 1891; there was also good evidence that the same criminal had murdered Ellen Dunworth, October 13, 1891; Alice Marsh, April 12, 1892; Emma Shrivell, April 12, 1892, and had attempted the life of Louie Harvey. The agent in all these cases was strychnine. There was no evidence as to what form of the poison was administered in the case of Clover, but Ellen Dunworth, who was found dying in the streets at 7.45 P.M., and died less than two hours afterwards, stated that a gentleman gave her “two drops” of white stuff to drink.
In the cases of Marsh and Shrivell, Neill Cream had tea with them on the night of April 11, and gave them both “three long pills;” half an hour after Neill Cream left them they were found to be dying, and died within six hours. From Marsh 7 grains, from Shrivell nearly 2 grains of strychnine were separated; the probability is that each pill contained at least 3 grains of strychnine. The criminal met Louie Harvey on the Embankment, and gave her “some pills” to take; she pretended to do so, but threw them away. Hence it seems probable that Neill Cream took advantage of the weakness that a large number of the population have for taking pills, and mostly poisoned his victims in this manner. Clover’s case was not diagnosed during life, but strychnine was found six or seven months after burial in the body. It may be mentioned incidentally that the accused himself furnished the clue which led to his arrest, by writing letters charging certain members of the medical profession with poisoning these poor young prostitutes with strychnine.
§ 390. Fatal Dose.—In a research, which may, from its painstaking accuracy, be called classical, F. A. Falck has thrown much light upon the minimum lethal dose of strychnine for various animals. It would seem that, in relation to its size, the frog is by no means so sensible to strychnine as was believed, and that animals such as cats and rabbits take a smaller dose in proportion to their body-weight. The method used by Falck was to inject subcutaneously a solution of known strength of strychnine nitrate, and, beginning at first with a known lethal dose, a second experiment was then made with a smaller dose, and if that proved fatal, with a still smaller, and so on, until such a quantity was arrived at, that the chances as determined by direct observation were as great of recovery as of death. Operating in this way, and making no less than 20 experiments on the rabbit, he found that the least fatal dose for that animal was ·6 mgrm. of strychnine nitrate per kilogramme. Cats were a little less susceptible, taking ·75 mgrm. Operating on fowls, he found that strychnine taken into the crop in the usual way was very uncertain; 50 mgrms. per kilo, taken with the food had no effect, but results always followed if the poison was introduced into the circulation by the subcutaneous needle—the lethal dose for fowls being, under those circumstances, 1 to 2 mgrms. per kilo. He made 35 experiments on frogs, and found that to kill a frog by strychnine nitrate, at least 2 mgrms. per kilo, must be injected. Mice take a little more, from 2·3 to 2·4 mgrms. per kilo. In 2 experiments on the ring adder, in one 62·5 mgrms. per kilo. of strychnine nitrate, injected subcutaneously, caused death in seven hours; in the second, 23·1 mgrms. per kilo. caused death in five days; hence the last quantity is probably about the least fatal dose for this particular snake.
These observations may be conveniently thrown into the following table (see next page), placing the animals in order according to their relative sensitiveness.[426]