Strychnina, B.P. Strychnine.
Related entry: Nux Vomica
C2H22N2O2 = 334.196.
Strychnine, C21H22N2O2, is the chief alkaloidal constituent of the seeds of Strychnos Nux-vomica, Linn. (N.O. Loganiaceae), Strychnos Ignatii, Bergius, and various other species of Strychnos. It is also official in the U.S.P. It may be obtained from the crushed, dried, ripe seeds by boiling and exhausting with very dilute hydrochloric acid, concentrating the solution, adding milk of lime, collecting the precipitated alkaloid and excess of lime, and exhausting with boiling alcohol, from which on cooling the strychnine is deposited; or the exhaustion may be effected by means of alcohol, the alcohol removed by distillation, the residue dissolved in acidified water, colouring and other matter precipitated by lead acetate and filtered out, the filtrate, after removal of lead by hydrogen sulphide, concentrated, and mixed with lime or magnesia, by which the strychnine is liberated; the collected precipitate and excess precipitant are exhausted with boiling alcohol, and the alkaloid separated by fractional crystallisation. For the further purification of the alkaloid, 11 parts of the finely powdered base are mixed with 60 parts of boiling water, and diluted nitric acid added, little by little, until a neutral or only slightly acid solution is obtained. From this solution the greater part of the salt separates on cooling, the remainder being obtained from the mother liquor on a second crystallisation. The alkaloid may be precipitated from an aqueous solution of the nitrate thus obtained, by ammonia, and then recrystallised from boiling alcohol. Strychnine occurs in the form of translucent, trimetric, odourless, colourless prisms, or as a white, crystalline powder, having an extremely bitter, afterwards metallic taste; it is anhydrous, and very poisonous. The aqueous solution is intensely bitter, the bitterness being discernible in a solution 1 in 700,000. The solutions are laevorotatory, and alkaline in reaction. Melting-point, 265° to 266°. Strychnine is precipitated by potassium hydroxide from its acid solutions, but an excess of the alkali does not dissolve it; ammonia, however, forms a precipitate soluble in excess, but crystallising out after a time. The salts, or slightly acid solutions of the alkaloid, are precipitated by the usual alkaloidal reagents even in very dilute solutions. Bismuth-potassium iodide gives a brown precipitate, 1 in 250,000; potassio-mercuric iodide, a white precipitate, 1 in 150,000; picric acid, a yellow crystalline precipitate, 1 in 20,000; potassium ferrocyanide, a white crystalline precipitate, 1 in 100,000; solution of iodine in potassium iodide gives a reddish-brown precipitate, 1 in 100,000; this last precipitate is soluble in alcohol, from which it may be recovered in characteristic microscopic crystals on slow evaporation. Concentrated hydrochloric acid has no effect upon the alkaloid. Fused with potassium hydroxide, strychnine yields quinoline and indol. Continued heating of the solution in concentrated sulphuric acid at 100° produces strychnine monosulphonic acid, C21H21N2O2HSO3.
Soluble in water (about 1 in 7000), boiling water (1 in 2500), alcohol (1 in 170), boiling alcohol (1 in 12), absolute alcohol (1 in 350), boiling absolute alcohol (1 in 40), chloroform (1 in 6), benzene (1 in 160); nearly insoluble in ether.
Action and Uses.—Strychnine has the action of a bitter in the mouth, increasing the appetite and so augmenting the flow of gastric juice. It is rapidly absorbed as it reaches the intestines, the alkaloid and its salts more readily so than the crude preparations of nux vomica. After absorption, strychnine exerts its characteristic effects upon the central nervous system. Through its action on the sensory portion of the cord, the reflexes are exaggerated, and the normal tonus of striped muscle increased. The medulla is similarly affected, the ordinary afferent stimuli producing exaggerated effects, so that the movements of respiration are deepened and quickened, peripheral vessels are constricted through stimulation of the vaso-motor centre, and the heart slowed through excitation of the vagal centre. The sense organs are stimulated, so that the senses of smell, touch, hearing and vision are rendered more acute. The blood pressure is raised by the vaso-constriction produced, so that strychnine improves the pulse and is a valuable tonic to the circulatory system in cardiac failure. On account of its action in augmenting the reflexes of the cord, strychnine is an aphrodisiac in the male and an emmenagogue in the female. It reflexly increases the tonus of plain muscle, and also has a direct stimulant effect, so that it is of value in such conditions as chronic constipation, atony of the bladder, etc. Strychnine is excreted very slowly, and its action is therefore cumulative in other than small doses. It is much used as a gastric tonic in dyspepsia, and as a general tonic in convalescence from acute disease; with atropine it is used in dipsomania, hypodermically, and by the mouth. The solution of the hydrochloride is administered in mixture form, often with mineral acids; or pills may be prepared by carefully triturating the alkaloid with milk sugar and massing with syrup of glucose. It is added to aperient pills to increase peristalsis, but preparations of nux vomica are often preferred for this purpose (see Nux Vomica). It is used in surgical shock and in cardiac failure, large doses, up to 6 milligrams (1/10 grain), being given by hypodermic injection. It is also added to solutions of local anaesthetics for high intraspinal injections (1/2 to 1 milligram) to prevent respiratory failure, but is not uniformly successful for this purpose. It is used as an antidote in chloral and chloroform poisoning. In cases of poisoning by strychnine, emetics or the stomach-pump should be used, and tannin or potassium permanganate administered to render the strychnine inactive. The convulsions are controlled by chloroform anaesthesia, or by large doses of chloral or bromide. The administration of urethane in large doses (10 to 20 grammes) is considered of value as an antidotal measure.
Dose.—1 to 4 milligrams (1/60 to 1/15 grain).
The British Pharmaceutical Codex, 1911, was published by direction of the Council of the Pharmaceutical Society of Great Britain.