Physostigma. U. S.

Physostigma. U. S.

Physostigma. Physostig. [Calabar Bean, Ordeal Bean]

"The dried ripe seeds of Physostigma venenosum Balfour (Fam. Leguminosae), yielding not less than 0.15 per cent. of the alkaloids of Physostigma." U. S.

Physostigmatis Semina, Br. 1898; Chopnut; Ordeal Bean of Calabar; Faba Calabarica; Feve du Calabar, Fr. Cod.; Kalabarbohne, G.; Haba del calabar, Eseve, Sp.

Physostigma venenosum is a climbing plant, with a ligneous stem, and frequenting especially the banks of streams, into which it often drops its fruit when ripe, and it is said that the people of Calabar derive their supply principally from the borders of the streams down which the fruits are carried. The rhizome is spreading, with numerous rootlets, often having attached to them small succulent tubers. The flowers are in axillary, multiflorous, pendulous racemes. The corolla is papilionaceous, of a pale pink color, with a purplish tinge. The legume when ripe is about seven inches long, and contains two or three seeds. It ripens at all seasons, but is most abundant during the rainy season from June to September. The seeds are the part used. The plant, which is indigenous to Western Africa, has been introduced into India and Brazil, and is said to flourish in the latter country. The market supplies are obtained from the regions surrounding the mouth of the Niger and the lower portion of the Calabar River, the chief port of export being Lagos (Ap. Ztg., xxvi, p. 568; xxvii, p. 137). Only one other species (P. mesoponticum Taub.., also of tropical Africa, is known. For a paper on the botanical description, history, etc., of Physostigma venenosum by J. U. Lloyd, see West. Drug., 1897, 249.

This bean was brought to the notice of the scientific public by Daniell, in 1846. Considerable attention was attached to the subject, and specimens of the bean were obtained by Christison from the Gold Coast. These were planted in the Botanical Garden at Edinburgh, and produced a perennial creeper. In the year 1859, specimens of the plant were sent from Calabar, which came under the observation of Balfour, of Edinburgh, who was thus enabled to ascertain its botanical character.

Properties.—The seeds are officially described as follows: "Oblong or ellipsoidal, somewhat compressed reniform, from 15 to 30 mm. in length and from 10 to 15 mm. in thickness; externally reddish or chocolate brown, smooth, somewhat wrinkled near the brownish-black groove, the latter being about 2 mm. in width and extending almost the entire length of the convex edge and in which are found frequently the remains of the white membranous funiculus, the margins of the seed-coat on both sides of the groove somewhat elevated, of a yellowish-red or brownish-red color and somewhat thickened; embryos large, white, with short hypocotyl and two concavo-convex cotyledons; taste at first starchy, afterwards acrid. The powder is grayish-white, starch grains numerous, from 0.005 to 0.15 mm. in diameter, ellipsoidal or somewhat reniform, and usually with a distinct cleft and frequently with radiating or irregular fissures; fragments of seed-coat with very thick, reddish-brown cells, being either palisade-like or very irregular and resembling stone cells, but the walls are not lignified; an occasional fragment with tracheae showing reticulate thickenings. Physostigma yields not more than 3 per cent. of ash." U. S.

Physostigmine was official in the Br. Pharm., 1885, and was thus described: "In colorless or pinkish crystals, slightly soluble in water, but readily soluble in alcohol and in diluted acids. The aqueous solution has an alkaline reaction, when warmed with or when shaken with dilute solution of potash becomes red, and when evaporated to dryness over a water bath leaves a bluish residue, the acidified solution of which is beautifully dichroic, being blue and red." Br., 1885.

Calabar beans are occasionally substituted by a number of more or less similar seeds of African plants. Hartwich (S. W. P., 1905, p. 441) calls attention to a false physostigma found in the Hamburg drug market which is derived from Pentaclet__ra macrophylla Benth., a leguminous tree indigenous to tropical Africa. The seeds are dark reddish-brown, from 5 to 7 cm. long, about 5 cm. broad and about 1 cm. thick. They are flattened-oval or roundish-triangular.

Physostigma yields its virtues to alcohol, and imperfectly to water. The shell constitutes, according to Edwards, 30 per cent., the kernel 70 per cent., of the bean. Jobst and Hesse (J. P. C., March, 1864, p. 277) first isolated an active principle, which they found exclusively in the cotyledons. They obtained it by exhausting an alcoholic extract of the seeds with water, adding magnesia to neutralization, which is indicated by the liquid becoming brown, then concentrating, and treating with ether. The ethereal solution was shaken with a little weak sulphuric acid. The liquid separated into two layers—the upper, ethereal, containing no alkaloid, and the lower, a solution of the sulphate in water. The latter was separated, treated with magnesia, and afterwards with ether, which yielded the alkaloid on evaporation. The substance thus obtained they proposed to name physostigmine. In 1865 Vee and Leven (C. R. A. S., 60, 1194) obtained, by treating the seeds in nearly the same manner, an alkaloid to which they gave the name eserine, which formed colorless tabular crystals of a bitter taste, readily soluble in ether, alcohol, or chloroform, but sparingly in water. The crystals contain 1 molecule of water, which they lose at 100° C. (212° F.), and the anhydrous alkaloid then fuses at from 102° to 103° C. (215.6 °-217.4° F.). Eserine is now generally accepted as identical with physostigmine. In 1867, Hesse (Ann. Ch. Ph., 141, 82) obtained the same alkaloid in a still purer state, perfectly colorless and tasteless, fusing at 45° C. (113° F.), and decomposing at 100° C. (212° F.) with red coloration. He gives it the formula C15H21O2N3.

A peculiarity of the alkaloid is that an aqueous solution of it, or of one of its salts, exposed to the air in the presence of potassium or sodium hydroxides, or lime, becomes red, owing to the absorption of oxygen. The coloring matter is taken up by chloroform. The color is not permanent, but gradually changes to yellow, green, or blue. This test will detect less than the hundred-thousandth part of the alkaloid. The same property is possessed by the alcoholic extract of the bean. This is the cause of the color changes taking place in solutions dispensed in ordinary glass bottles. The change may be retarded by previously rinsing out the bottle with diluted hydrochloric acid, and subsequently with distilled water, or it may be entirely prevented by coating the inner surface of the dispensing vial with paraffin.

Harnack and Witkowski (A. E. P. P., v; also x) in 1876 obtained still another alkaloid, which they named calabarine. It is soluble in alcohol and water, nearly insoluble in ether, melts at 132° C. (269.6° F.), and differs in physiological character from physostigmine. It is now generally known under the name of eseridine. The formula C15H23O3N3 has been given to it by Eber (Ph. Ztg., 1888, p. 611), which differs from that of physostigmine, it will be seen, by H2O only, and it is stated that the one can be changed into the other by the action of dilute acids. It has properties like eserine but in a milder degree. Eseramine, C16H25O3N4, is another alkaloid of feeble activity which is present. It was announced by Ehrenberg in 1893 (Verhand. d. Gesellsch. Deutsche Natur. u. Aertzte., 1893, ii, p. 102). There is much reason for believing that calabarine is a decomposition product derived from physostigmine. (Husemann, A. E. P. P., 1878, 14; Harnack, A. E. P. P., x.)

Still another alkaloid announced by Salway is physorenine, C14H18O3N2. It is a powerful myotic like eserine. It is believed to be an intermediate product in the decomposition of eserine by alkalies, which results in the formation of a new base called eseroline, C13H18ON2. Another decomposition product of eserine is produced by an excess of ammonia and is called eserine blue, C17H23O2N3.

Hesse obtained also a neutral fatty body, plhysosterin, by exhausting the cotyledons with petroleum benzin. It is closely allied to cholesterin, but its chloroform solution? is devoid of rotatory power. Its formula is C26H44O + H2O, and its melting point is 133° C. (271.4° F.).

Uses.—The action of physostigma is practically that of its dominant alkaloid physostigmine, but the effects are more or less modified by the other alkaloids; thus calabarine is a stimulant to the spinal cord and in this regard antagonistic to physostigmine, while isophysostigmine possesses the physiological properties of the dominant alkaloid upon the unstriped muscle, but apparently not upon the other structures of the body. For this reason whenever the systemic action is desired the alkaloid should be given the preference over preparations of the whole drug. On the other hand, as a stimulant to the unstriped muscle of the intestines, as in constipation, the whole drug may properly be used.

Poisoning.—Calabar bean has been used from time immemorial by the natives of Africa as an ordeal, and, when given by their head men, usually proves fatal to the accused, unless free vomiting occurs. A draught containing 19 seeds pounded and infused in water is said to have killed a man in an hour. In the experiments of Fraser, it was found that the integuments of the seeds, as well as the shell, are distinctly purgative. It is probable that in the fresh bean they are also emetic, and that the priests or chiefs who administer the ordeal take advantage of this in regulating the effects of the poison to suit their own purposes; sometimes, however, even the pure alkaloid causes vomiting. (Gubler.) Of seventy children poisoned in Liverpool by eating Calabar beans which had been thrown upon a waste heap, vomiting occurred, or was produced by emetics, in all except one, in whom four kernels caused death. The nausea and vomiting came on in about half an hour, the nervous symptoms in less than an hour.

There are generally diminution of reflexes, coarse muscular tremors which may be sufficiently violent to suggest convulsions, contraction of the pupil, and progressive diminution of motor power. In the fatal cases death is generally due to paralytic asphyxia.

In the treatment of physostigma poisoning the stomach should be thoroughly washed out either with an emetic or the stomach pump. and tannic acid or compound solution of iodine given as a chemical antidote. Atropine, which is a partial physiological antagonist, should be given in doses of about one-fiftieth of a grain (0.0013 Gin.), and strychnine and other stimulants employed as indicated.

Dose, one to three grains (0.065-0.2 Gm.).

Off. Prep.—Extractum Physostigmatis,U. S.; Tinctura Physostigmatis, U. S.


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