Active Ingredients. - The efficient element of Calabar bean is the alkaloid called eserine or physostigmine, C15H11N3O2: it is present only in the cotyledons of the seeds. Physostigmine 1 is a colorless varnish-like stuff which dries with heat into thin scales, but at ordinary temperatures soon softens again. It is said, when exceedingly pure, to form crystalline crusts, or even glittering rhombic scales. It is tasteless, and decidedly alkaline in reaction: easily soluble in alcohol, ether, benzol, and chloroform: not very soluble in water. If heated for a long time, at 212° F., it alters to a reddish color, and its solutions in acid are now red. It can be identified at once by these characters, together with the physiological action on the pupil to be presently described.

Physiological Action - The most curious and characteristic action of Calabar bean is one that renders it of extensively useful application in ophthalmic medicine and surgery; this is contraction of the pupil and of the ciliary muscle. It induces a condition of short-sightedness, and occasions sympathetic dilatation of the pupil of the other eye. A difficulty is found, however, in regard to the preparations, since the alcoholic extract, which contains the whole of the poisonous principle, can be only imperfectly dissolved in water (the alcoholic solution being of course, per se, inadmissible), while the flow of tears, which instantly follows such an application, greatly reduces the amount placed in contact with the membrane, or at any rate renders it very uncertain. Hence it is found useful to employ the extract diffused in bibulous paper after the manner that has been recommended for the application of atropine; while another mode is to use a solution of the extract in glycerine, the latter in no way interfering with its operation. The proportion is 2 1/2 grs. of extract to 100 minims of pure glycerine. Another very useful plan is to impregnate gelatine with calabar extract and to place a minute disc of this material within the eyelids, where it dissolves.

Calabar bean has, however, much wider actions on the body than have yet been mentioned. The researches of Christison, Fraser, and others in this country, and of a number of German and French observers, have illustrated these actions with much fulness. Perhaps the best summary that has been given of the action of the Calabar bean on the heart and spinal nervous system is that of Roeber: 2 "1. The chief action of the bean consists of a depression and final annihilation of the excitability of the ganglionic elements of the spinal cord; and its operation especially affects the groups of cells in the anterior horns of the gray matter which conduct impulses from the brain to the periphery, and then also attacks the elements of the gray matter in the posterior horns which transmit

1 While this is actually going through the press, I am informed, on the best authority, that physostigmine has been discovered to possess one property which is entirely opposed to the action of the bean itself. It paralyzes, instead of stimulating, the terminals of the vagus. (1874. ) sensations of pain to the brain. 2. By this functional lesion of the gray matter a complete loss of the motor and reflex activity of the spinal cord is produced, likewise a loss of sensibility to pain; while the sense of touch, and the so-called muscular sense, are retained till the death of the animal. 3. Besides this action on the cord, Calabar bean possesses a special power over the movements of the heart, which in small doses it merely retards, but in large doses completely arrests. 4. The interference with respiration, which is especially produced by small doses, is either the consequence of a sudden interference with the heart's action, or is produced by a destruction of the motor power of the respiratory muscles from paralysis of the spinal cord. 5. The poison increases the secretion of tears and of saliva. 6. The increase of defecation observed in poisoning with Calabar bean is the result of a tetanus of the stomach and intestines, the cause of which is not yet fully determined. 7. The motor and sensory nerves are not affected at the commencement or in the development of the affections of the cord: at a latter stage there follows a paralysis or hastened death of the intra-muscular termini of these nerves. 8. The fibrillary muscular twitchings occurring soon after the administration of the poison, which are especially striking in mammalia, may be explained by a local irritation of them, caused by paralysis of the motor nervi-termini. 9. The pupils are strongly contracted both in the external and in the internal use in large doses of Calabar bean extract: but as to the cause of this it will be necessary to institute more exact inquiries.

2 Ueber die Wirkung des Calabar-extractes auf Herz u. Ruckenmark. Inaug. Diss. von Hermann Roeber. Berlin, 1868. In Practitioner, 1869, vol. ii.

But the most interesting properties are those, perhaps, which place physostigma in opposition to belladonna, or, more accurately speaking, to atropia, upon which subject Dr. Thomas R. Fraser has recently printed a most valuable and copious monograph, which is also to be seen in the Transactions of the Royal Society of Edinburgh (vol. xxvi. p. 529,1872). Dealing first with the general idea of antagonism in medicines, he shows it to be necessary, when the action of a particular poison or other energetic substance has to be counteracted, that the physiological functions of the affected organism should be modified; - a principle early, though very imperfectly, recognized in the original employment of alexipharmics. More exact knowledge has led to the discovery that organic modifications of a definite and constant character can be established; that the modifications produced by certain drugs are exactly the reverse of those produced upon the same part by certain other drugs; such, for example, is the case in the action exerted upon the iris by opium or morphia on the one hand, and by hyoscyamus, belladonna, and strampnium on the other. The contrary and opposite action of physostigma and atropia Dr. Fraser shows to be exactly of this character. His researches, commenced in 1868, have been followed up steadily to the present time, and have consisted of a vast number of carefully tabulated experiments, chiefly upon rabbits; and the conclusive deduction is that the lethal action of physostigma finds a powerfully counteracting one in the influence of atropia. That is to say, the fatal effects of a lethal dose of physostigma are neutralized by the employment of atropia (under certain conditions of administration), the atropia so influencing certain structures as to prevent the occurrence in them of the modifications induced by physostigma, which, if not so dealt with, would result in death. The action of physostigma is cancelled by that of atropia, and so decided is the antagonism that so large a quantity even as 3 1/2 times the minimum lethal dose of the physostigma is rendered inoperative. Dr. Fraser, however, had in some, degree been anticipated as early as 1864, when Kleinwachter narrated a case of belladonna-poisoning, which had been successfully treated by phy-sostigma. In Paris, also, a case of tetanus had been much ameliorated by the internal administration of the powdered kernel of physostigma - enough, it was believed, to cause death - followed up by the subcutaneous injection of a small quantity of atropia. Dr. Fraser's own experiments disclose facts of a very singular character. For instance, when the two substances (physostigma and atropia) are administered simultaneously, they induce certain actions of intensity sufficient to cause death; whereas, if the administration of the physostigma be delayed for 25 minutes after that of the atropia, those actions cease to be fatal ones. To delay the administration of the physostigma for only 5 minutes, or, with the same respective doses, for only 10 minutes, is still insufficient to ward off death: recovery from the influence of the atropia takes place only at a minimum of 15 to 20 minutes. The counteracting effect of atropia in regard to the lethal action of physostigma, is successfully exerted, moreover, only within a definite range of doses, determinable by experiment.