Physostigma (U. S. P.)—Physostigma.

Fig. 192. Physostigma venenosum. Preparations: Tincture of Physostigma - Extract of Physostigma
Related entries: Curare.—Woorari - Strophanthus (U. S. P.)—Strophanthus - Nux Vomica (U. S. P.)—Nux Vomica: arrow poison

"The seed of Physostigma venenosum, Balfour"— (U. S. P.).
Nat. Ord.—Leguminosae.
COMMON NAMES: Calabar bean (Faba calabarica), Ordeal bean of Calabar.

Botanical Source.—This is a large, herbaceous, climbing perennial, with the stem woody at the base, about 2 inches in diameter, twining, and sometimes 50 feet long. The leaves are large and pinnately-trifoliate; and the leaflets ample, ovate, and acuminate, with stipels. The flowers are large, about an inch long, in pendulous, fascicled racemes, on axillary peduncles, pale-pink or purplish, and beautifully veined. The bracts generally fall early, and the flower-stalk or rachis is covered with tuber-like knots. Corolla crescentiform, papilionaceous; vexillum round-ovate, recurved; apex bilobed, base angustate, margins auriculate; alae oblong-obovate, free, incurved; keel obovate and produced into a twisted beak. The calyx is campanulate, quadrifid, 5-toothed, short, broad, the two upper nearly united. Upper stamens free; anthers all alike. Ovary raised on a stipe, 2 or 3-ovuled. Style thickened within the beak of the keel, and twisted with it, bearded along the inner side, and bearing a hood-like appendage at the apex covering the stigma. The legume is broad-linear, flattened, but convex on both sides, 2-valved, and slightly constricted between the seeds, which are oblong, with a long, linear hilum.

Fig. 193. Calabar bean. History.—This plant, the Ordeal bean of Calabar, is a native of Calabar, in the Gulf of Guinea, on the western coast of Africa, and, according to Dr. Mery, around the sources of the river Coma, near Gabon. It is the only known species of the genus, unless we include the Mucuna cylindrosperma, Welwitsch, by some called Physostigma cylindrospermum, whose seeds were found with the commercial drug by Holmes, in 1879. It grows along the banks of rivers, climbing upon the adjacent trees and shrubs, and when the seeds become ripe they frequently fall into the rivers, are carried down the stream, and collected by the natives residing on the borders. The Calabar negroes call the seed eséré, and use it as an ordeal for the purpose of deciding the guilt or innocence of persons accused of crimes. It has been a very difficult matter to procure these beans, as the natives were averse to giving them to foreigners, hence their high price. In this connection, see a more detailed account of the Calabar bean and its uses, by J. U. Lloyd, in the Western Druggist, 1897, p. 249. Calabar bean is a violent poison, but did not attract attention on the part of the medical profession until its power of contracting the pupil of the eye was discovered. The first important notice on the subject was made by Dr. Christison before the Royal Society of Edinburgh, February 5,1855, and which is published in their proceedings. Dr. Thomas R. Fraser was the first to discover, in 1862, its peculiar property of contracting the pupil, and subsequently Dr. Argyll Robinson made a more complete analysis of its ophthalmic properties. The present botanical name of the plant was given to it by Dr. Balfour, of Edinburgh. The powder, the tincture, specific physostigma, eserine, and the extract of Calabar bean (see Extractum Physostigmatis) are employed for internal use.

Description.—The bean or seed is the part used, and is officially described as "about 25 to 30 Mm. (1 to 1 ¼ inches) long, 15 to 20 Mm. (⅗ to ¾ inch) broad, and 10 to 15 Mm. (⅖ to ⅗ inch) thick; oblong, and somewhat reniform; testa granular, chocolate-brown, with a broad, black groove extending over the entire length of the convex edge; embryo with a short, curved radicle, and 2 large, white, concavo-convex cotyledons; inodorous; taste bean-like. On moistening the embryo with potassium hydrate T.S., it becomes pale-yellow"—(U. S. P.). The latter test serves to distinguish this bean from that of Physostigma cylindrospermum, which produces with the alkali an almost orange color, turning to greenish (see E. M. Holmes, Pharm. Jour. Trans., Vol. IX, 1879, p. 913). The average weight of the seed is about 4.1 grammes (63 grains). Alcohol takes up its virtues entirely, water but partially. The kernel is brittle and constitutes the most poisonous part of the seed, the episperm being nearly inert; but it is exceedingly difficult to completely separate the latter.

Chemical Composition.—Calabar bean contains starch (48 per cent), mucilage, albumen (23 per cent,), fatty oil (2.5 per cent), and salts, mainly potassium phosphate. The chief active principle of physostigma is the alkaloid physostigmine, discovered, in 1864, by Jobst and Hesse. Vée and Leven (1865) claimed to have obtained it in crystallized form, and named it eserine, from ésére, the African term for the ordeal bean. Jobst and Hesse prepared it by treating an alcoholic extract of the seeds with solution of sodium bicarbonate, and shaking out the alkaloid with ether, abstracting it with diluted sulphuric acid and again treating this solution with sodium bicarbonate and ether. The French Codex uses the name eserine exclusively.

PHYSOSTIGMINE (C15H21N3O2) (Eserine) forms colorless, hygroscopic, thin plates, slightly soluble in water, easily soluble in alcohol, ether, chloroform, benzol and carbon disulphide. It is strongly basic, and forms salts with acids, some of which are crystallizable. Physostigmine is an unstable body when exposed to light and air, and especially at a higher temperature (100° C. or 212° F.), it turns red, and is converted into Duquesnel's rubreserine (C13H16N2O2, Ehrenberg, 1894), a deep-red substance insoluble in ether, but soluble in chloroform. Free alkali and ammonia favor this change, while sodium bicarbonate hardly affects the alkaloid. The salts of physostigmine yield precipitates with alkaloidal reagents (see color reactions under Physostigminae Sulphas and Salicylas). This alkaloid is too poisonous for general use. It may cause death when absorbed by the conjunctiva; the of a grain injected hypodermatically, or 1/16 of a grain introduced into the stomach, will, with the adult, cause symptoms of intolerance; a larger dose will produce graver symptoms. It is not a counter-poison to strychnine. It merely changes the symptoms of the poisoning and the results of the autopsy without retarding the death.

A second alkaloid, calabarine, was discovered in Calabar bean, in 1876, by Harnack and Witkowski, distinguished from eserine principally by its being insoluble in ether. It is soluble in alcohol and water, and its toxic power is about one-sixth that of eserine. It resembles strychnine in its physiological action more nearly than physostigmine, producing tetanic movements in animals of the lower order. Ehrenberg (Chem. Centralblatt, 1894, p. 439) believes that calabarine is a decomposition product of physostigma alkaloids. Eber, in 1888, found in the Calabar bean an alkaloid, eseridine (C15H23N3O3), distinguished by its property of liberating iodine from iodic acid. Ehrenberg (loc. cit.) finally isolated the crystallizable alkaloid, eseramine (C16H25N4O3), which is physiologically inactive. By extracting Calabar bean with petroleum ether, Hesse (18718) obtained phytosterin, a substance closely related to the alcohol cholesterin in animal fats.

Action, Medical Uses, and Dosage.—Calabar bean, when administered in poisonous doses to animals, appears to produce a depressing influence, as manifested by a slight tremor, followed by paralysis of the limbs, slow and irregular respiration, with stertor, muscular twitchings, more or less complete loss of sensation, contraction of the pupils, frothy mucus escapes from the mouth, and finally there is only a gasping inspiration previous to death. Consciousness is preserved during the whole time, until the power of expression is lost. Reflex action can not be produced by either pricking or pinching the skin. Immediately after death the pupils dilate. With 45 children who were accidentally poisoned by the Calabar bean and taken to the Southern Hospital of Liverpool, the more prominent symptoms were loss of mobility, extreme prostration, slowness and feebleness of pulse, profuse sweats, coldness of the extremities, vomitings, and with some, severe diarrhoea. One of the children died, with whom there was neither nausea nor vomiting. These symptoms, with most of the children, disappeared in the course of 6 or 7 hours. Some look upon Calabar bean as a respiratory poison causing asphyxia; others, as interfering with contractions of the heart and producing syncope. Calabar bean appears to be a spinal paralyzer, lessening excitability of the peripheral extremities of the motor nerves, destroying excitability of the muscles, and directly diminishing reflex action. Its action on blood-vessels is, firstly, to contract them; secondly, to dilate them. It diminishes the pulsations of the heart (Fraser). Retention of the urine is sometimes produced owing to the sphincter contraction induced by the drug.

There is no known antidote to poisoning by Calabar bean except atropine, which should be injected in 1/30 grain doses; one indispensable condition is an evacuation of the poison; for, when used as an ordeal among the Calabar negroes, those who vomit do not die; so it was with the children above referred to. As to other measures, they must be based upon general principles according to the symptoms presenting, such as artificial respiration, electricity, coffee, stimulants, etc.

Calabar bean was introduced into medical practice as a valuable local agent in certain conditions of the eyes, since which it has been successfully employed internally in certain nervous disorders. The alcoholic extract of the bean was the preparation formerly used in ophthalmic practice as a local application to the eye, while at the present day the alkaloid eserine has largely supplanted the use of the extract; when brought into contact with the conjunctiva, physostigmine causes lachrymation, and in about 5 minutes later contraction of the pupil, followed by contraction of the ciliary muscles; this contraction reaches its height in half an hour, and continues for about 12 hours (sometimes less pronounced for days), without, however, producing complete immobility of the pupil. It counteracts the effect of atropine, and also acts if there is paralysis of the pupil. The contraction of the pupil and ciliary muscle thus produced, generally causes pain, which may be very severe and continue for hours. If the eye be used, or efforts at accommodation be made, the pain increases. It appears, according to the views of some observers, to act by depressing the functions of the spinal cord, and thus preventing the transmission of nervous impulses through the cord to and from the iris; others, however, believe that it does not primarily affect the spinal axis, but acts directly upon the muscles and their controlling nerves. The pupillary contraction is thought to be due to dilatation of the blood vessels supplying the iris. The effects of physostigmine may be confined to the eye to which it is applied. It has been successfully employed as a local application in mydriasis, from atropine or other cause, in iritis and inflammations of neighboring structures, when desirable to produce alternate contraction and dilatation of the pupils, thus preventing adhesions; paralysis of the ciliary muscle, retinitis with photophobia, photophobia with strumous ophthalmia, granular and irritable lids, ulceration of the margin of the cornea, prolapsus of the iris, and in all cases where pupillary contraction is indicated, or where it is desired to improve the accommodative power of the eye for distant vision. Glaucoma is palliated by the use of physostigmine, especially if it be induced by the use of atropine. It is a remedy for episcleritis. In corneal ulcerations with feeble recuperative powers, in indolent, nonvascular, corneal ulcers, and in hypopyon ulcers, it is extremely valuable.

Physostigmine is the agent to be selected to control excessive ocular tension after traumatisms. It subdues neuralgic pains in the eyeball, sometimes relieves convergent strabismus, and is often employed to overcome spasm of the muscles of accommodation when persistent. Gelatin discs of physostigmine (Lamellae Physostigminae) containing about 1/1000 grain of the alkaloid are occasionally used, and readily dissolve when placed upon the conjunctiva of the lower lids. The local effect ceases in from 12 to 24 hours. Generally, the solution (1 in 1000) is employed. A glycerin solution (1 part in 5) of the extract was formerly, and is still used to some extent.

The internal administration of the extract has also been found useful in chorea, centric or eccentric tetanus, epilepsy, reflex neuralgia, reflex paralysis, etc. However, its therapeutical effects in these diseases, are not fully decided. It is, however, a useful remedy in diseases of the brain and spinal cord, when administered in minute doses, the usual prescription being: Rx Specific physostigma gtt. v, aqua ℥iv. Mix. Dose, a teaspoonful every 2 to 4 hours. The indications for its use here are a cool surface, cold extremities, feeble, tremulous pulse, and contracted pupils. Occasionally the dilated pupil will lead to its use if the associate symptom is a rapid, small, tense pulse. Dullness of intellect, pupillary contraction, and the small, weak pulse are the symptoms of cerebro-spinal meningitis, which call for its exhibition. The same state of the pulse with a forcible upturning of the eyes, points to its use in puerperal convulsions, which it sometimes relieves. Larger doses than for the above-named nervous conditions are required in tetanus. As large a dose as 5 drops of specific physostigma may be repeated every 1 or 2 hours in this complaint.

In one case of traumatic tetanus, Watson gave 2 grains every hour. Fraser does not think the powder advisable in tetanus, the functions of the stomach being considerably impaired in this disease. The ordinary tincture is an uncertain preparation, and should not be used. The alcoholic extract must be administered with great care; its commencing dose should not exceed ⅗ of a grain in 24 hours, and at no time should its dose exceed 2 grains in 24 hours. It may be given in pill form, or dissolved in diluted alcohol, spirit, wine, or glycerin. Watson advises a preparation made by dissolving 8 grains of the alcoholic extract in ½ fluid ounce of boiling water, then gradually adding 1 ½ fluid ounces of alcohol, and filtering; 10 minims of this contain 1/12 of a grain of the extract, which is a good dose to begin with in an adult. When used in subcutaneous injection the extract may be rubbed up in water, and a little chloride of sodium or a few drops of liquor potassae be added. In a severe case of traumatic tetanus, Ashdown made use of a subcutaneous injection of ⅓ of a grain of the extract in 18 minims of water; repeating the injection every 2 hours. But great care is required in determining the amount of extract necessary in any given case; when physostigmine is employed for this purpose, a solution of 1 part to 1000 is amply sufficient, of which a few drops only should be injected, repeating the operation according to the effects produced.

Physostigmine has also been proposed as an antagonist to poisoning by belladonna or atropine. I have found its internal use decidedly successful in several cases of impotence, the result of masturbation, also in cases of imperfect erection with premature seminal discharge on attempting coition; in which affections I am not aware its use has been heretofore tested. The dose of the powder is usually about 4 or 6 grains, during the 24 hours, in water, emulsion, or pill form (J. King). Extract of physostigmine (1/10 grain) and eserine (1/60 grain) have been successfully employed in excessive sweating, while the internal use of the former has been suggested in cholera, diarrhoea, fecal accumulation due to intestinal dilatation, and in gastralgia, chronic constipation, intestinal, renal, and cystic catarrh, phthisical night sweats, dyspnoea, emphysema, bronchial dilatation, and asthma. Commencing dose of the extract, 1/10 grain; of the powder, 1 grain; for specific uses in nervous diseases, a fraction of a drop of specific physostigma; for other purposes a fraction of a drop to 5 drops; of eserine, 1/100 grain, carried as high as 1/25 grain; for local ocular purposes, a few drops of a solution of eserine (1 in 1000); for hypodermatic use, a solution of eserine (1 in 1000).

Specific Indications and Uses.—Eserine: Locally to induce contraction of the pupil in mydriasis or injuries to the eye; iritis, corneal ulcers, iridal prolapse, and ocular inflammations. Physostigma: Pulse feeble and tremulous, surface cool, extremities cold, and pupils contracted; or pupils dilated with small, rapid, tensive pulse; mental torpor in cerebro-spinal meningitis; breathing difficult with sense of constriction.

Related Drugs and Substitutions.—ANTIARIS, Upas antiar. A gummy-resinous exudate from Antiaris toxicaria, Leschenault (Nat. Ord.—Urticaceae). The tree furnishing this poison is one of the large forest trees of Java, Celebes, and the islands near by. It is well known on account of the term Deadly upas applied to it, for it is said to exhale, like the poisonous species of Rhus, a volatile matter which affects some individuals, causing swellings and eruptions upon the skin. The milk-white or yellowish exudate flows when the tree is wounded; this upon exposure becomes brownish in color. It forms the bulk of the Upas antiar or so-called Javanese arrow-poison, and is identical with the Ipoh poison of the Malays (see Nux Vomica). Upas antiar is a waxy, reddish-brown body having an acrid, and excessively bitter taste. Alcohol and ether partially dissolve it; with water it forms an emulsion. It contains besides albumen, wax, and guru, the following peculiar principles: (1) The toxic, crystallizable, glucosid, antiarin (C27H42H10+4H2O, Kiliani, 1896), discovered in 1824 by Pelletier and Caventou; it is soluble in 27.4 parts of boiling alcohol, in 254 parts of water at 22.5° C. (79.5° F.), and in 2792 parts of ether (Mulder). It has a high melting point (225° C. or 437° F., Kiliani). When heated with diluted hydrochloric acid, it is decomposed into antiarigenin and antiarose, isomeric with rhamnose (Kiliani). (2) Antiarol (C9H12O4, Kiliani), soluble in warm water, melting at 146° C. (294.8° F.). (3) Antiaresin (C24H36O, Kiliani), crystallizing from hot alcoholic solution in long needles, melting at 173.50 C. (344.3° F.) (see Jahresb. der Pharm., 1896, p. 46).

The effects of upas antiar and antiarin are decidedly different from those produced by other bodies also known as upas. Thus the Upas Tieuté (which see) gives the tetanizing effects of strychnine, which it contains. Upas antiar does not appear to act upon the brain or spinal axis, but upon voluntary and involuntary muscles and the larger nerve trunks. It does not produce convulsions or tetanize, but all voluntary movements are impaired or wholly suspended by it according to the amount of the poison absorbed. Even small doses act upon the vasomotor centers, producing increased arterial tension, while large doses paralyze the heart muscle, death taking place from this effect. In effects it more closely resembles physostigma than any other agent, but has not yet been applied therapeutically.

CANJOURA.—The seeds of a creeper of Salvador, from which the inhabitants prepare a paste, said to act violently upon the nervous system. A state of delirium lasting a week or more is said to have been induced by it. ("Bouea oblongifolia" (USDisp) - Can't find such a plant in the botanical databases - Henriette)

CALI NUTS, or CALI BEANS.—These are worthless substitutes for Calabar beans, mostly derived from certain papilionaceous plants of the genus Entada, e. g., E. scandens (see article with illustration by W. B. Hay, in the Western Druggist, 1898, p. 101). They bear no resemblance to Calabar beans (see articles on Cali beans in Chem. Zeitung, 1887, p. 633; 1890, p. 34; 1891, p. 823).

King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.