[408] Compt. Rend., lix. p. 406, 1864.
[409] See J. Bouchardat, La Narcéine, Thèse, Paris, 1865; Harley, The Old Vegetable Neurotics, Lond.; Ch. Liné, Études sur la Narcéine et son Emploi Thérapeutique, Thèse, Paris, 1865; also, Husemann’s Planzenstoffe, in which these and other researches are summarised.
§ 372. Papaverine (C21H21NO4) crystallises from alcohol in white needles or scales. It possesses scarcely any alkaline reaction, but its salts have an acid reaction; it has but little effect on a ray of polarised light. It is almost insoluble in water; it is easily soluble in acetone, amyl alcohol, alcohol, and chloroform. One part of the alkaloid is dissolved in 36·6 of benzene, and in 76 parts of amyl alcohol. Petroleum ether dissolves it by the aid of heat, but the alkaloid separates in crystals on cooling. Chloroform extracts it from either acid or alkaline solutions. Papaverine gives no crystalline sublimate. The melting-point of pure samples in a tube is 147°, with scarcely any colour; it solidifies again to crystals on cooling; in the subliming cell it melts at 130°, and decomposes about 149°; the vapours are alkaline; the residue is amorphous, light brown, and is not characteristic. Concentrated sulphuric acid colours it a deep violet-blue, and dissolves it to a violet, slowly fading. This solution, by permanganate of potash, is first green and then grey. Fröhde’s reagent gives a beautiful violet colour, which becomes blue, and vanishes after twenty-four hours. Diluted solutions of salts of papaverine are not precipitated by phosphomolybdic acid. It is precipitated by ammonia, by the caustic and carbonated alkalies, by potassic-cadmic iodide, iodine in hydriodic acid, and by alkaloidal reagents generally—save by the important exception mentioned above. A solution in amyl alcohol is also precipitated by bromine; the precipitate is crystalline. An alcoholic solution of platinic chloride also separates papaverine platin chloride in crystals. An alcoholic solution of iodine, added to an alcoholic solution of papaverine, separates in a little time crystals of the composition C21H21NO4I3. From the mother-liquor, by concentration, can be obtained needles of another iodine combination, C21H21NO4I5; the latter heated above 100° parts with free iodine. These compounds with iodine are decomposed by ammonia and potash, papaverine separating. The decomposition may be watched under the microscope. Nitric acid precipitates from a solution of the sulphate a white nitrate soluble in excess; the precipitate does not appear at once, but forms in the course of an hour; it is at first amorphous, but subsequently crystalline; this, with its physical properties, is a great assistance to identification.
§ 373. Effects.—Claude Bernard ranked papaverine with the convulsants; probably the papaverine he had was impure. In any case, subsequent observations have shown that it is to be classed rather with the hypnotic principles of opium. Leidesdorf[410] administered it to the insane, and noted slowness of the pulse, muscular weakness, and drowsiness to follow. The doses were given subcutaneously (·42 grm. of the hydrochloride). Baxt,[411] experimenting with the frog, found that a milligramme caused deep sleep and slowing of the heart’s action. This action on the heart is witnessed also on the recently-removed frog’s heart. Guinea-pigs, and other small animals poisoned by strychnine or thebaine, and then given papaverine, did not seem to be so soon affected with tetanus as when no such remedy was administered. The fatal dose of papaverine for a man is unknown. I should conjecture that the least quantity that would cause dangerous symptoms would be 1 grm. (15·4 grains).
[410] Ztschr. d. Wien. Aerzte, pp. 13, 115, 1868.
[411] Arch. Anat. Phys., p. 70, 1869.
§ 374. Thebaine, C17H15NO(OCH3)2.—Opium seldom contains much more than 1 per cent. of this alkaloid. It usually forms needles or short crystals. It is alkaline, and by rubbing becomes negatively electric. It is almost insoluble in water, aqueous ammonia, and solutions of the alkalies. It requires 10 parts of cold alcohol for solution, and dissolves readily in hot. Ether, hot or cold, is also a good solvent. 100 parts of benzene are required for 5·27 parts of thebaine, and 100 of amyl alcohol for 1·67 parts. Chloroform dissolves thebaine with difficulty out of both acid and alkaline solutions; petroleum ether extracts it from neither. Thebaine melts in a tube at 193°, sublimes at 135°. The sublimate is in minute crystals, similar to theine; at higher temperatures (160° to 200°) needles, cubes, and prisms are obtained. The residue is fawn coloured. Fröhde’s reagent (as well as concentrated sulphuric acid) dissolves it, with the production of a blood-red colour, passing gradually into yellow. The precipitate with picric acid is yellow and amorphous; with tannic acid yellow; with gold chloride, red-yellow; and with platinic chloride, citron-yellow, gradually becoming crystalline. A concentrated alcoholic solution of thebaine, just neutralised with HCl, deposits well-formed rhombic crystals of the composition C19H21NO3HCl + H2O.