Preparation: Ointment of Strychnine - Pills of Aloin, Strychnine, and Belladonna
Related entries: Ignatia.—Ignatia - Nux Vomica (U. S. P.)—Nux Vomica - Strychninae Sulphas (U. S. P.)—Strychnine Sulphate
FORMULA: C21H22N2O2. MOLECULAR WEIGHT: 333.31.
"An alkaloid obtained from Nux vomica, and also obtainable from other plants of the natural order Loganiaceae"—(U. S. P.).
History and Preparation.—Strychnine was discovered by Pelletier and Caventou. (1818) in St. Ignatius beans (see Ignatia), and, subsequently, also in nux vomica and other species of Strychnos, always accompanied by the alkaloid brucine. The latter is more soluble in boiling water and diluted alcohol than strychnine, and brucine nitrate is more soluble in water than strychnine nitrate. These differences permit separation of both alkaloids. Strychnine is obtained almost exclusively from the seeds of nux vomica. A practical difficulty consists in the toughness of the seeds. These are previously exposed to heat, then powdered; or the seeds are softened by prolonged boiling with diluted sulphuric acid (Merck). The process of the British Pharmacopoeia (1885) consists in extracting the powdered seeds by prolonged digestion with diluted alcohol, distilling off the alcohol, precipitating igasuric acid with lead acetate, evaporating the filtrate, and adding aqua ammoniae to slight excess, drying the precipitate, and extracting it with alcohol. Upon evaporation of the solvent, the bulk of strychnine crystallizes first; it is obtained pure by recrystallization. (For a summary of other methods, see Husemann and Hilger, Pflanzenstoffe, 1884, p. 1284.)
Description.—The U. S. P. thus describes strychnine: "Colorless, transparent, octohedral, or prismatic crystals, or a white, crystalline powder, odorless, and having an intensely bitter taste, perceptible even in highly dilute (1 in 700,000) solution. Permanent in the air. Soluble, at 15° C. (59° F.), in 6700 parts of water, and in 110 parts of alcohol; in 2500 parts of boiling water, and in 12 parts of boiling alcohol. Also soluble in 7 parts of chloroform, but almost insoluble in ether"—(U. S. P.). It is also insoluble in caustic alkalies, moderately soluble in fixed and volatile oils and creosote, in amyl alcohol (181 parts), benzol (164 parts), and glycerin (300 parts) (compare the solubilities of brucine, under Nux Vomica). "When heated to 268° C. (514.4° F.), strychnine melts. Upon ignition, it is consumed, leaving no residue. Strychnine has an alkaline reaction upon litmus paper"—(U. S. P.). With acids, it forms crystallizable salts of an intensely bitter taste. Chemically, strychnine is a derivative of the base quinoline (C6H4:C3H3N), and is still under investigation. (For the quantitative separation of strychnine and brucine, see Nux Vomica.) Another method recommended by Gordin and Prescott (Amer. Jour. Pharm., 1899, p. 18), is that of Dunstan and Short (ibid., 1883, p. 5719), which consists in precipitating strychnine with potassium ferrocyanide from solution slightly acidulated with sulphuric acid. Brucine is precipitated only in concentrated solution.
The solutions of strychnine in diluted acids are precipitated by all alkaloidal reagents. Mercuric chloride occasions a white precipitate, composed of plumose tufts and acicular, radiating crystals. Platinum chloride and gold chloride produce pale-yellow crystals. Picric acid will occasion a pale-yellow precipitate of very delicate needles, arranged in tufts or in radii. Potassium iodide produces a rich amber-yellow or reddish-brown precipitate, composed of minute prisms. Chloride of iron, perchloric acid, iodine, tannic acid, potassium chromate and bichromate, ammonia water, potassa, soda, and potassium and sodium carbonates, each, produce a precipitate; hence, all of these reagents are incompatible with salts of strychnine. This alkaloid enters into a crystallizable compound with iodoform (Amer. Jour. Pharm., 1882, p. 119). It also combines with chloroform, but not unless the solution is heated, in a sealed tube, to 120° C. (248° F.), and higher (P. F. Trowbridge, Archiv der Pharm., 1899, p. 624) Strychnine resists putrefactive influences exceedingly well. Dr. Riekher (Neues Jahrbuch der Pharm., Vol. XXIX, 1868, p. 1) was able to determine its presence in the heart, lung, and liver of a steer, after the specimens had been kept for 11 years in loosely-covered jars, under the roof of a house. (Also see G. Welborn, Proc. Amer. Pharm. Assoc., 1893, p. 865.)
Tests.—The most characteristic test for strychnine is the violet-blue color, produced with strong sulphuric acid and oxidizing agents. With cold sulphuric acid alone, pure strychnine produces a colorless solution. The U. S. P. gives the following directions for the color test, and for the limit of brucine: "If a minute quantity of strychnine be dissolved in about 0.5 Cc. of concentrated sulphuric acid on a white porcelain surface, and a small crystal of potassium dichromate slowly drawn across the liquid with a glass rod, there will be produced at first, momentarily, a blue color, which quickly changes to purplish-blue, then gradually to violet, purplish-red, and cherry-red, and finally to orange or yellow. On dissolving 0.02 Gm. of strychnine in 2 Cc. of nitric acid (specific gravity 1.300), in a small test-tube, the acid should not turn more than faintly yellow (limit of brucine)"—(U. S. P). (Regarding the latter test, see brucine, under Nux Vomica.) The blue coloration in the strychnine test is also obtained by other oxidizers, e.g., dioxide of manganese (MnO2), of lead (PbO2), potassium permanganate, etc., and the reaction is exceedingly delicate, being obtainable with 1/100 milligramme of alkaloid, provided brucine is absent. The presence of large quantities of brucine interferes with the reaction (see Flückiger-Nagelvoort, Reactions, Detroit, 1893; and H. Beckurts, Archiv der Pharm., 1892, p. 551; also see Dr. T. G. Wormley's work on the Micro-Chemistry of Poisons, 1885, pp. 542-612).
Salts of Strychnine.—STRYCHNINAE CITRAS, Citrate of strychnine, may be made by dissolving, with a gentle heat, in a sufficient quantity of distilled water, 192 parts of dried citric acid, and then adding 346 parts of pure strychnine. By gentle evaporation the citrate may be obtained in crystals. The above proportions correspond to an acid salt (C6H8O7.C21H22N2O2). The dose is from 1/10 to 1/20 grain, to be given cautiously till the desired effect is produced.
STRYCHNINAE TARTRAS, tartrate of strychnine, may be obtained by dissolving in a sufficient quantity of distilled water, 1,56 parts of tartaric acid, and then adding 346 parts of strychnine, and evaporating as above. It is also an acid salt, and has the formula C4H6O6.C21H22N2O2+3H2O (Arppe). The dose is the same as for the citrate.
STRYCHNINAE ACETAS, Strychnine acetate.—This solution forms crystals, which, when evaporated in solution, lose a portion of their acid. It does not easily crystallize. Soluble in chloroform (about 15 parts) and in water (96 parts).
STRYCHNINAE HYDRIODAS, Strychnine hydriodate (C21H22N2O2.HI)—To solution of a salt of strychnine add solution of potassium iodide. Collect the precipitate, dissolve it in alcohol, and allow to crystallize. It forms very bitter, 4-angled needles, or white scales; dissolves but sparingly in water at ordinary temperatures, but dissolves quite readily in alcohol. The salt holds 72.2 per cent of the alkaloid.
STRYCHNINAE HYDROCHLORAS, Strychnine hydrochlorate (2[C21H22N2O2.HCl]3H2O).—Dissolve strychnine in warm diluted hydrochloric acid, and allow to cool. Silky, acicular crystals, containing per cent of the alkaloid. Soluble in cold water (50 parts); loses its water of crystallization quite readily.
STRYCHNINAE NITRAS, Strychnine nitrate (C21H22N2O2.HNO3).—Dissolve strychnine in warm diluted nitric acid, and allow to cool. Extremely bitter, colorless needles are formed, which contain 84 per cent of strychnine. It dissolves in cold water (90 parts), boiling water (3 parts), cold alcohol (70 parts), boiling alcohol (5 parts), and glycerin (26 parts); somewhat soluble in fixed oils and absolute alcohol, not soluble in ether and carbon disulphide. This agent is official in the Ger. Pharm. It has been largely used in the treatment of the alcohol habit.
STRYCHNINAE HYDROBROMAS, Strychnine hydrobromate (C21H21N2O2.HBr).—This salt contains 80.4 per cent of the base. It crystallizes in prismatic needles, easily soluble in diluted alcohol, but sparingly in strong alcohol. Water (32 parts) effects its solution. According to Bullock, it is prepared by the interaction of strychnine sulphate and potassium bromide in diluted alcoholic solution, whereby potassium sulphate forms an insoluble precipitate. The reaction is as follows: (C21H22N2O2)2.H2SO4+2KBr=K2SO4+2C21H22N2O2.HBr.
STRYCHNINAE PHOSPHAS, Strychnine phosphate (1/100 to 1/10 grain), has been advised in pregnancy, when the patient is exhausted of anemic (see Ellingwood's Mat. Med. and Therap., pp. 169 and 170). Prepared by dissolving strychnine in phosphoric acid.
STRYCHNINAE ARSENIAS, Strychnine arseniate, may be given, in doses of 1/200 to 1/80 grain, in debility and prostration of the aged, or those suffering from the effects of severe disease. It possesses, in an increased proportion, the antimalarial effects of strychnine. Prepared by dissolving strychnine in aqueous arsenic acid (AsO4H3).
King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.