Veratrina. U. S. Veratrine.
"A mixture of alkaloids obtained from the seed of Asagraea officinalis (Chamisso and Schlechtendal) Lindley (Fam. Liliaceae). Preserve it in well-closed containers, protected from light." U. S.
Veratrine, Fr. Cod.; Veratrinum, P. G.; Veratrin, G.; Veratrina. It., Sp.
No process is given in the U. S. P. IX for preparing veratrine and the Br. Pharm., 1914, deleted it. A process will be found in the U. S. D., 19th edition, pages 1327 and 1328.
In the U. S. process of 1870 the first step is to obtain a tincture of cevadilla, which is evaporated to the consistence of an extract. This contains the veratrine combined with a vegetable acid, probably gallic, as it exists in the seeds. From the extract the alkaloid is dissolved by the acidulated water, which at the same time converts it in great measure into a sulphate, a small portion possibly remaining in the solution combined with an excess of the natural acid. The magnesia combines with the acids and throws down the veratrine, which is then taken up by alcohol and again yielded in a purer state by evaporation. To purify it still further, it is redissolved in water by the agency of sulphuric acid, is submitted to the action of animal charcoal, and is finally precipitated by ammonia. In the British process, the tincture was concentrated until it began to let fall a precipitate, and was then poured into water, which throws down the resin and oil with a portion of the coloring matter and retains the salt of veratrine. This is then decomposed by ammonia, and the precipitated veratrine is slightly washed with cold water to free it from adhering impurities. If much water be employed in the washing, a considerable portion of the veratrine will be lost, in consequence of impure veratrine being in some degree soluble in water. The remaining steps of the British process consist in the purification of the veratrine by forming a hydrochloride in solution, decolorizing this by animal charcoal and again precipitating by ammonia.
The U. S. process of 1870 is essentially that of Couerbe. The veratrine obtained by it, though not pure, is sufficiently so for medicinal use. A drachm of it, in this state, may be procured from a pound of cevadilla. Meissner, in 1819, applied the term sabadilline to an alkaloid extracted by him. Pelletier and Caventou had probably produced the same preparation when they announced the discovery of veratrine in the same year. This substance is the veratrine described as prepared by Couerbe's process. Couerbe, in 1834, announced the discovery of an additional alkaloid, to which he gave Meissner's old name of sabadilline, and Weigelin, in 1871, announced the discovery of a third alkaloid, which he called sabatrine. G. Merck, in 1855, obtained veratrine in a crystallized state by solution and separation from strong alcohol.
Wright and Luff (J. Chem. S., 33, p. 338) have brought order from this confusion by a careful study of the whole subject. They found three alkaloids in sabadilla seeds: cevadine, C32H49O9N (the alkaloid hitherto known as the veratrine of Merck); veratrine, C37H53O11N; and cevadilline, C34H53O8N. Of these, the cevadine (formerly veratrine) forms, when crystallized from alcohol, needles or compact crystals which fuse at 205° C. (401° F.), effloresce rapidly in the air, and become opaque, are insoluble in water, easily soluble in alcohol and ether, and dissolve in warm concentrated hydrochloric acid with a dark violet color, which on boiling becomes intensely red. When heated with alcoholic potassium hydroxide they are decomposed into methyl-crotonic (tiglinic) acid and cevine, C27H43O8N. The veratrine of Wright and Luff is obtained from the mother liquor of the cevadine by extraction with ether. It forms an uncrystallizable resinous mass, fusing at 180° C. (356° F.), but yields crystallized salts. Boiled with sodium hydroxide it is decomposed into dimethyl-protocatechuic (veratric) acid and verine, C28H45O8N. Cevadilline remains after the extraction of the veratrine, insoluble in ether. It is also uncrystallizable, nearly insoluble in ether and in boiling benzene, but easily soluble in fusel oil.
Flückiger recognized only two of these alkaloids, and made them both of the composition C32H49O9N. The first, which he called cevadine, he stated is decomposed by boiling with barium hydroxide when in alcoholic solution, and yielded products as follows: C32H49O9N + 2H2O = C5H8O2 + C27H45O9N
The first of these products is methyl-crotonic acid, and the second is cevine. The other alkaloid he called veratridine, and gave its decomposition as follows: 2C32H49O9N + 4H2O = C9H10O4 + C55H92O16N2 + 2H2O
The first of these products is dimethyl-protocatechuic acid, and the second he called veratroin. (Flückiger, Pharm. Chem., 1888, ii, p. 532.) Merck still terms the cevadine of Wright and Luff veratrine, and prepares it in white crystals of the formula C32H49O9N, fusing at 202° C. (395.6° F.). Frankforter (A. J. P., 1897, 372) confirmed this formula, C32H49O9N.H2O, but gave to the purified veratrine the melting point from 146° to 148° C. (294.8° - 298.4° F.).
Two acids have also been found in sabadilla—the sabadillic or cevadic acid of Pelletier and Caventou, forming needle-like crystals fusing at 20° C. (68° F.), and the veratric acid of Merck, which Koerner showed to be dimethylproto-catechuic acid.
Uses.—Probably because of its unfortunate name it has been assumed by some that veratrine represents the therapeutic virtues of veratrum. Its physiological action, however, differs greatly from that of veratrum, and if it possess any therapeutic usefulness it is certainly not for the conditions for which veratrum is employed.
Veratrine is an intense local irritant and somewhat locally anesthetic. Rubbed upon the skin it excites a sensation of warmth and a peculiar tingling. Sometimes an evanescent blush is produced and still more rarely an eruption upon the skin, but generally no decided signs of inflammation are evinced. When taken into the mouth it produces an almost insupportable sense of acrimony, and snuffed up the nostril it produces violent sneezing, and when taken into the stomach in large doses it causes violent vomiting, serous purging with intense burning in the mouth and throat and general muscular weakness. It is a powerful muscle poisoning and if given in sufficient dose in the lower animals it causes an extraordinary prolongation of the contraction of the striated muscles; the time required for relaxation of voluntary muscles may be 20 or 30 times as long as normal. A similar influence is exerted upon the ventricular muscles, at least in the frog, but the slowing of the heart rate seen in warm blooded animals seems to be due chiefly to stimulation of the cardio-inhibitory center. Death in mammals is generally due to depression of the respiration.
The only justifiable therapeutic use of veratrine is as an anodyne counter-irritant in neuralgias and various forms of arthritis. Even for this purpose it has no advantages sufficient to offset the dangers of systemic poison which might follow from its absorption.
Dose, one-thirtieth of a grain (0.002 Gm.).
Off. Prep.—Oleatum Veratrinae, N. F.; Unguentum Veratrinae, N. F.
The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.