Nux Vomica. U. S., Br.

Nux Vomica. U. S., Br.

Nux Vomica. Nux Vom. [Strychni Semen, P. I.]

"The dried, ripe seeds of Strychnos Nux-vomica Linné (Fam. Loganiaceae), yielding not less than 2.5 per cent. of the alkaloids of Nux Vomica." U. S. "Nux Vomica consists of the dried ripe seeds of Strychnos Nux-vomica, Linn." Br.

Semen Nucis Vomicae; Poison Nut, Quaker Buttons, Dog Buttons; Noix vomique, Fr. Cod.; Semen Strychni, P. G.; Krähenaugen, Brechnuss, G.; Noce vomica, It.; Nuez vomica, Sp.

Strychnos Nux-vomica is a tree of a moderate size, with numerous strong branches, covered with a smooth, dark gray bark. The young branches are long, flexuous, smooth, and dark green, with opposite, roundish-oval, petiolate, entire, smooth, and shining leaves. The flowers are small, white, funnel-shaped and in terminal corymbs. The fruit is a round berry, about as large as an orange, with a smooth, yellow or orange-colored, hard, fragile rind, and many seeds in a juicy pulp. It has frequently been asserted that the pulp is innocuous, but Fluckiger and Hanbury, and also Dunstan and Short (P. J., 3d series, xv, 1) have demonstrated that it contains strychnine. Dunstan and Short have also proved that of the commercial varieties of nux vomica Bombay seed stands first in percentage of contained strychnine, then Cochin, and lastly Madras. (P. J., 1883, xiv, 1053.)

The tree is a native of the East Indies, growing in Bengal, Malabar, on the Coromandel Coast, in Ceylon, in many islands of the Indian Archipelago, in Cochin China, and in Northern Australia. The drug is largely shipped from Madras, where it is estimated that in 1912 nearly 400,000 pounds were marketed. Much of the nux vomica shipped to the United States is exported from Bombay, and in 1910-1911 some 45,000 pounds of nux vomica were exported to the United States from the Bombay district. The chief markets for nux vomica are China, and America, small quantities are shipped to London, and the importations to Hamburg are very irregular. Joblin states that during the fiscal year 1909 there were imported into the United States 1,666,957 pounds of nux vomica; in 1910, 2,738,662 pounds. (Cons. & Tr. Rep., 1911, p. 350.)

The wood and root are very bitter, and are employed in the East Indies for the cure of intermittents. The radices colubrinae and lignum, colubrinum of the older writers, long known in Europe as narcotic poisons, have been ascribed to this species of Strychnos, under the impression that they were identical with Strychnos colubrina, to which Linnaeus refers them. They were ascertained by Pelletier and Caventou's researches to contain a large quantity of strychnine. The bark has been mistaken for cusparia, and hence is sometimes referred to as false angustura. Gehe & Co. (Handelsbericht, 1914, p. 119) state that a new variety of nux vomica, the origin of which is unknown, is being exported from Burma. The seeds are externally light gray, internally yellow and are devoid of strychnine.

Properties.—Nux vomica is officially described as "orbicular, nearly flat, occasionally irregularly bent, from 10 to 30 mm. in diameter and from 4 to 5 mm. in thickness, very hard when dry; externally grayish or greenish-gray, covered with appressed hairs giving it a silky luster, hilum indicated by a circular sear at the center of one of the flattened sides and connected with the micropyle at the edge by a ridge; internally showing a thin, hairy seed-coat and a large grayish-white endosperm at one end of which is embedded a small embryo with two broadly ovate, 5- to 7-nerved cotyledons; inodorous; taste intensely and persistently bitter. The powder is light gray; consisting chiefly of thick-walled endosperm cells containing globules of a fixed oil and a few small aleurone grains, and fragments of strongly lignified, non-glandular hairs, the walls of the latter possessing large, circular, or long, slit-like pores. In the tissues of the adhering pulp occur a few small, nearly spherical starch grains. Nux Vomica yields not more than 3.5 per cent. of ash." U. S.

"Seeds disc-shaped, nearly flat, but sometimes irregularly bent; rounded or somewhat acute at the margin, from a small prominence on which a raised line passes to the central hilum. Ash-grey or greenish-grey. From two to two and a half centimetres in diameter, and about six millimetres thick. Surface densely covered with short, satiny, radiately arranged and closely appressed hairs. Endosperm large and horny; cotyledon small and leafy. Powdered Nux Vomica exhibits fragments of the endosperm, the cell-walls of which are very thick but not lignified, also slender rod-like fragments of the hairs and their thickened, pitted, lignified basal portions. No odor; taste extremely bitter. Yields not less than 1.25 per cent. of strychnine when tested by the following process." Br.

The seeds are destitute of odor, but have an acrid, very bitter taste, which is much stronger in the kernel than in the investing membrane. They impart their virtues to water, but more readily to diluted alcohol. For a method of distinguishing powdered nux vomica from powdered ignatia and other powders, see Proc. A, Ph. A., 1897, 503.

Herder has proposed a detection of the alkaloids in nux vomica by various microchemical means and shows how they may be localized in the seeds and growing plants. (A. Pharm., 1906, p. 129.) Tunmann (A. Pharm., 1910, 644) has studied the distribution of the alkaloids in the germinating seeds of Strychnos Nux vomica, and concludes that the embryo of the seed contained only brucine and that strychnine, which was contained in the endosperm only in the cell plasma of the cell content, appears to act as a protection for the growing plant. Grutterink has also published an illustrated article on the microchemical examination of the several alkaloids of nux vomica. (Zeit. An. Chem., li, p. 187.) Rushy has reported the shipment of nux vomica which consisted of small inferior seeds which had been rolled in some mixture of clay. (Proc. A. Ph. A; 1908, lvi, p. 794.) Powdered nux vomica has been adulterated with ground olive stones and the raspings of vegetable ivory. (See Rep. d. Pharm,., 1909, p. 241; Ann. d. chim. Analyt., 1909, p. 261.)

The chemists Pelletier and Caventou discovered in nux vomica two alkaline principles, strychnine and brucine, united with a peculiar acid which they named igasuric. Its other constituents are a yellow coloring matter, a fixed oil, grun, starch, a small quantity of wax, and several earthy phosphates. Charles Bullock, in preparing the alcoholic extract of nux vomica with a moderate continuous heat, so as to dry it sufficiently to be pulverized, separated from 150 pounds of the seeds 5 pints of a liquid oil. This oil has a saponification number of 124, and an iodine number of 64 to 67. The unsaponifiable portion of the oil was identified as a mixture of phytosterin. (A. Pharm., 1912, p. 398.) F. Meyer (In. Dis., St. Petersburg, 1875) investigated the fatty oil from nux vomica, and found it to consist of the glycerides of capric, caprylic, caproic, butyric, and palmitic acids. (A. J. P., 1874, 405.) Shenstone (J. Chem. S., xxxix, 453) has shown that the igasurine of Desnoix is a mixture of strychnine and brucine. A glucoside, loganin, has also been found in the nux vomica seeds, but it exists more largely in the surrounding pulp. Dunstan and Short, its discoverers (P. J. 1883, xiv, 1025), gave to it the formula C25H34O14. Boorsma stated that he had discovered a new alkaloid in the leaves of S. Nux vomica (Bull. de l'Inst. Bot. de Buitenzorg) and he named it strychnicine; it is only slightly poisonous. (See also P. J., 1902, 65.)

Hugo H. Schafer (J. A. P. A., 1914, p. 1077) announces a new alkaloid in nux vomica which he has named struxine. This alkaloid is stated to have the chemical formula C21H30C4N2. It is present only in the drug coming from Cochin China, and was found in an amount of 0.1 per cent.

Igasurine was said to be found in the mother waters from which strychnine and brucine have been precipitated by lime. Jorgensen believed that it was identical with brucine (see A. J. P., June, 1872, p. 257), and W. A. Shenstone confirmed this view. (A. J. P., Dec., 1881.)

Loganin is present in the pulp to the amount of 4 or 5 per cent., and is contained in small quantity also in the seeds. It was obtained by exhausting the pulp with a mixture of chloroform and alcohol (100:25). The exhaustion was effected in an apparatus for hot repercolation. The percolate, on cooling, deposited crystals, which when recrystallized a number of times from alcohol, and finally from absolute alcohol, were obtained pure. Loganin is easily soluble in water and alcohol, less soluble in ether, chloroform, and benzene. Its aqueous solution is not precipitated by any of the alkaloidal reagents. Its most characteristic reaction is found in its behavior with concentrated sulphuric acid. A very small quantity of loganin, when gently warmed with a few drops of concentrated sulphuric acid, yields a fine red color, which, on standing, develops into a deep purple. By boiling with dilute sulphuric acid, loganin is resolved into glucose (reducing Fehling's solution) and a body for which the name loganetin is proposed. This substance, like loganin, gives the characteristic reaction with sulphuric acid, but the purple color does not develop so rapidly. Loganetin is soluble in water and alcohol, less soluble in ether, carbon disulphide and chloroform. (P. J., 1884, p. 1025.)

Strychnine (C21H22O2N2) was discovered by Pelletier and Caventou in 1818, in both the nux vomica and the bean of St. Ignatius, and received its name from the generic title of the plants (Strychnos) to which these two products belong. According to these chemists, it exists much more abundantly in the bean of St, Ignatius than in the nux vomica, the former yielding 1.2 per cent., the latter only 0.4 per cent., of strychnine, but Dragendorff obtained from nux vomica from 1.9 to 2.1 per cent. of mixed alkaloids, about half of which was strychnine. (Jahresbericht, 1874, 103.) For valuable practical information about the yield of the alkaloids, extracts, etc., by E. L. Patch, see Proc. A. Ph. A., 1891, 91; also P. J., 1889, 341; Proc. Michigan Pharm. Assoc., 1889; Proc. Ohio Pharm. Assoc., 1889; P. J., 1890, 493.

Other species of Strychnos contain the poisonous alkaloids, and may some time become a commercial source of them. Bidara laut of the Indian bazaars, believed to be obtained from S. ligustrina, has been analyzed by Russow, who found the wood to contain 2.26 per cent. and the bark 7.38 per cent. of brucine without strychnine. Henry Q. Greenish found in the wood and bark respectively of S. colubrina 0.96 per cent. and 5.54 per cent. of mixed alkaloids; the same analyst obtained from false Angustura bark (S. Nux vomica), young bark 3.10 per cent., old bark 1.68. (P. J., 3d ser., ix, 1014.) According to Bernelot-Moens, the dry seeds of the S. tieute contain 1.469 per cent. of strychnine, with a trace of brucine. (A. J. P., 1866, p. 506.) From the seeds of Strychnos Rheedii W. R. Dunstan obtained a yield of 0.06 per cent. of brucine and no strychnine. (Imp. Inst. Rep., 1901-1902.) The Congo poison known as Cupua Apus, according to Vinci (A. I. P. T., xx), is produced from the Strychnos kipapa. The bark of the root contains 6 per cent. of strychnine and the wood 0.1 per cent.

Brucine (C23H26O4N2) was discovered by Pelletier and Caventou, first in the bark called false Angustura, in combination with gallic acid, and subsequently, associated with strychnine in the form of igasurates, in the nux vomica and the bean of St. Ignatius. It is crystallizable from alcohol, the crystals then containing 4H2O. It is without odor, but of a permanent, harsh, very bitter taste; is soluble in 850 parts of cold and in 500 of boiling water; very soluble in alcohol, whether hot or cold; it dissolves in 4 parts of chloroform, 440 parts of ether, 60 parts of benzene, and 120 parts of petroleum benzin. It is permanent in the air, but melts at a temperature a little above that of boiling water, and on cooling congeals into a mass resembling wax. The hydrated crystals melt at 115° C. (239° F.), and sublime at 204° C. (399.2° F.), while the anhydrous base melts at 178° C. (352.4° F.), changing color, and depositing carbon. (P. J., 1868, 375.) It forms crystallizable salts with acids. Concentrated nitric acid produces with brucine or its salts an intense crimson color, which changes to yellow by heat, and upon the addition of stannous chloride becomes violet. A test for brucine, given by Stanislas Cotton, consists in adding to a warm solution of brucine (from 40° to 50° C. (104°-122° F.)) in nitric acid, a concentrated solution of sodium thiosulphate. The mixture first becomes violet, and then passes to green when the alkaline salt is in excess. (J. P. C; Juillet, 1869, 18.) These effects serve to distinguish brucine from strychnine, and, if produced with the latter alkaloid, evince the presence of the former. According to Larocque and Thibierge, auric chloride produces, with solutions of the salts of brucine, precipitates at first milky, then coffee-colored, and finally chocolate-brown. (Journ. de Chim. Med., Oct., 1842.) Chlorine water produces with solution of brucine a rose color, due to the formation of dichlor-brucine. This is a reddish-brown, hygroscopic powder. (A. Pharm., 1886, 934.) A dinitro-brucine, C23H24(NO2)2N2O4, has also been obtained by the action of nitrogen trioxide upon the brucine in alcoholic solution. Brucine appears to bear a definite relation to strychnine in chemical constitution, being a dimethoxy-strychnine. According to the analyses of Shenstone and Dragendorff, the bark of the nux vomica contains brucine, with a trace of strychnine, while in the leaves Hooper found only brucine. (P. J., 1890, xxi.)

Brucine may be procured from false Angustura bark, in a manner essentially the same as that in which strychnine is procured from nux vomica, with this difference, that the alcoholic extract obtained from the precipitate produced by lime or magnesia should be treated with oxalic acid, and subsequently with a mixture of rectified alcohol and ether, which takes up the coloring matter, leaving brucine oxalate. This is decomposed by magnesia, and the brucine is separated by alcohol, which by spontaneous evaporation yields it in the state of crystals. Prescott (Organic Analysis, 1887, p. 458) gives two methods for the separation of strychnine from brucine; first, by the use of alcohol of 0.97 sp. gr., which easily dissolves brucine, but has very slight solvent power upon strychnine; second, by Dunstan and Short's method with potassium ferrocyanide. This method has been reported upon by Hoist and Beckurts (Ph. Centralh., N. P., 1887, p. 119), who find that if the hydrochloric acid solution containing mixed alkaloids is not too dilute, on the addition of potassium ferrocyanide the whole of the strychnine will be precipitated as ferrocyanide, while the brucine salt will remain in solution.

The separation of brucine from strychnine is most conveniently effected by exposing the mixed alkaloids to the action of diluted nitric acid, which destroys brucine very rapidly while having no appreciable action on strychnine; this method is used in the former official assay process.

Igasuric acid has been regarded as erroneously named, and investigators have stated that it was malic acid and tannic acid, while Q. Sander (A. Pharm., 1897, 133) believes that the acid found in nux vomica, heretofore known as igasuric acid, is caffeo-tannic acid.

Uses.—The medicinal and toxic properties of nux vomica are those of its alkaloid. (See Strychnina.) The belief held by some physicians that it acts more favorably as a bitter upon the stomach has only this much of justification—namely, that it is more slowly absorbed, and therefore acts locally somewhat more persistently.

BRUCINE.—On account of the difficulty of separating strychnine from brucine, it has been found by physiologists difficult to determine the exact action upon the human organism of the pure alkaloid. It was formerly taught that brucine closely resembled strychnine in its physiological action, except that it was less poisonous and that it was depressant to the peripheral sensory nerves. Dickson and Harvey (P. J., 1908, lxxxi, p. 367), however, experimenting with a chemically pure brucine, reach the conclusion that its dominant action is a paralysis of the peripheral motor nerves, and that the convulsive action which is the characteristic effect of strychnine is almost entirely absent in the case of brucine. According to the observation of Mays, brucine is an active paralyzant to the sensory nerves and a 5 or 10 per cent. solution applied to the mouth causes local anesthesia. He has used it for the relief of pruritus. Bumett also asserts that a 5 per cent. solution is a valuable local anodyne in inflammations of the external ear.

Dose, of nux vomica, one to four grains (0.065-0.26 Gm.).

Off. Prep.—Extractum Nucis Vomicae (from Liquid Extract), U. S., Br.; Fluidextractum Nucis Vomicae, U. S. (Br.); Tinctura Nucis Vomicae (from Extract), U. S. (from Liquid Extract), Br.; Elixir Phosphori et Nucis Vomicae (from Tinctura), N. F.; Pilulae Aloes et Podophylli Compositae (from Extract), N. F.; Pilulae Ferri, Quininae, Aloes et Nucis Vomicae (from Extract), N. F.; Pilulae Laxativae Post Partum (from Extract), N. F.

The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.