# 1911 Encyclopædia Britannica/Calabar Bean

CALABAR BEAN, the seed of a leguminous plant, Physostigma venenosum, a native of tropical Africa. It derives its scientific name from a curious beak-like appendage at the end of the stigma, in the centre of the flower; this appendage though solid was supposed to be hollow (hence the name from φῦσα, a bladder, and stigma). The plant has a climbing habit like the scarlet runner, and attains a height of about 50 ft. with a stem an inch or two in thickness. The seed pods, which contain two or three seeds or beans, are 6 or 7 in. in length; and the beans are about the size of an ordinary horse bean but much thicker, with a deep chocolate-brown colour. They constitute the E-ser-e or ordeal beans of the negroes of Old Calabar, being administered to persons accused of witchcraft or other crimes. In cases where the poisonous material did its deadly work, it was held at once to indicate and rightly to punish guilt; but when it was rejected by the stomach of the accused, innocence was held to be satisfactorily established. A form of duelling with the seeds is also known among the natives, in which the two opponents divide a bean, each eating one-half; that quantity has been known to kill both adversaries. Although thus highly poisonous, the bean has nothing in external aspect, taste or smell to distinguish it from any harmless leguminous seed, and very disastrous effects have resulted from its being incautiously left in the way of children. The beans were first introduced into England in the year 1840; but the plant was not accurately described till 1861, and its physiological effects were investigated in 1863 by Sir Thomas R. Fraser.

The bean usually contains a little more than 1% of alkaloids. Of these two have been identified, one called calabarine, and the other, now a highly important drug, known as physostigmine—or occasionally as eserine. The British pharmacopoeia contains an alcoholic extract of the bean, intended for internal administration; but the alkaloid is now always employed. This is used as the sulphate, which has the empirical formula of (C15H21N3O2)2, H2SO4, plus an unknown number of molecules of water. It occurs in small yellowish crystals, which are turned red by exposure to light or air. They are readily soluble in water or alcohol and possess a bitter taste. The dose is ${\displaystyle {\tfrac {1}{60}}}$ - ${\displaystyle {\tfrac {1}{30}}}$ grain, and should invariably be administered by hypodermic injection. For the use of the oculist, who constantly employs this drug, it is also prepared in lamellae for insertion within the conjunctival sac. Each of these contains one-thousandth part of a grain of physostigmine sulphate, a quantity which is perfectly efficient.

Physostigmine has no action on the unbroken skin. When swallowed it rapidly causes a great increase in the salivary secretion, being one of the most powerful sialogogues known. It has been shown that the action is due to a direct influence on the secreting gland-cells themselves. After a few minutes the salivation is arrested owing to the constricting influence of the drug upon the blood-vessels that supply the glands. There is also felt a sense of constriction in the pharynx, due to the action of the drug on its muscular fibres. A similar stimulation of the non-striped muscle in the alimentary canal results in violent vomiting and purging, if a large dose has been taken. Physostigmine, indeed, stimulates nearly all the non-striped muscles in the body, and this action upon the muscular coats of the arteries, and especially of the arterioles, causes a great rise in blood-pressure shortly after its absorption, which is very rapid. The terminals of the vagus nerve are also stimulated, causing the heart to beat more slowly. Later in its action, the drug depresses the intra-cardiac motor ganglia, causing prolongation of diastole and finally arrest of the heart in dilatation. A large lethal dose kills by this action, but the minimum lethal dose by its combined action on the respiration and the heart. The respiration is at first accelerated by a dose of physostigmine, but is afterwards slowed and ultimately arrested. The initial hastening is due to a stimulation of the vagus terminals in the lung, as it does not occur if these nerves are previously divided. The final arrest is due to paralysis of the respiratory centre in the medulla oblongata, hastened by a quasi-asthmatic contraction of the non-striped muscular tissue in the bronchial tubes, and by a "water-logging" of the lungs due to an increase in the amount of bronchial secretion. It may here be stated that the non-striped muscular tissue of the bladder, the uterus and the spleen is also stimulated, as well as that of the iris (see below). It is only in very large doses that the voluntary muscles are poisoned, there being induced in them a tremor which may simulate ordinary convulsions. The action is a direct one upon the muscular tissue (cf. the case of the gland-cells), since it occurs in an animal whose motor nerves have been paralysed by curare.

Consciousness is entirely unaffected by physostigmine, there being apparently no action on any part of the brain above the medulla oblongata. But the influence of the alkaloid upon the spinal cord is very marked and characteristic. The reflex functions of the cord are entirely abolished, and it has been experimentally shown that this is due to a direct influence upon the cells in the anterior cornua. It is precisely the reverse of the typical action of strychnine. Near the termination of a fatal case there is a paralysis of the sensory columns of the cord, so that general sensibility is lowered. The alkaloid calabarine is, on the other hand, a stimulant of the motor and reflex functions of the cord, so that only the pure alkaloid physostigmine and not any preparation of Calabar bean itself should be used when it is desired to obtain this action.

Besides the secretions already mentioned as being stimulated, the bile, the tears and the perspiration are increased by the exhibition of this drug.

There remains only to consider its highly important action upon the eye. Whether administered in the form of the official lamella or by subcutaneous injection, physostigmine causes a contraction of the pupil more marked than in the case of any other known drug. That this action is a direct and not a nervous one is shown by the fact that if the eye be suddenly shaded the pupil will dilate a little, showing that the nerves which cause dilatation are still competent after the administration of physostigmine. Besides the sphincter pupillae, the fibres of the ciliary muscle are stimulated. There is consequently spasm of accommodation, so that clear vision of distant objects becomes impossible. The intra-ocular tension is markedly lowered. This action, at first sight somewhat obscure, is due to the extreme pupillary contraction which removes the mass of the iris from pressing upon the spaces of Fontana, through which the intraocular fluids normally make a very slow escape from the eye into its efferent lymphatics.

There is a marked antagonism in nearly all important particulars between the actions of physostigmine and of atropine. The details of this antagonism, as well as nearly all our knowledge of this valuable drug, we owe to Sir Thomas Fraser, who introduced it into therapeutics.

The clinical uses of physostigmine are based upon the facts of its pharmacology, as above detailed. It has been recommended in cases of chronic constipation, and of want of tone in the muscular wall of the urinary bladder. It has undoubtedly been of value in many cases of tetanus, in which it must be given in maximal doses. (The tetanus antitoxin should invariably be employed as well.) Sir Thomas Fraser differs from nearly all other authorities in regarding the drug as useless in cases of strychnine poisoning, and the question must be left open. There is some doubtful evidence of the value of the alkaloid in chorea. The oculist uses it for at least six purposes. Its stimulant action on the iris and ciliary muscle is employed when they are weak or paralysed. It is used in all cases where one needs to reduce the intra-ocular tension, and for this and other reasons in glaucoma. It is naturally the most efficient agent in relieving the discomfort or intolerable pain of photophobia; and it is the best means of breaking down adhesions of the iris, and of preventing prolapse of the iris after injuries to the cornea. In fact it is hardly possible to over-estimate its value in ophthalmology. The drug has been highly and widely recommended in general paralysis, but there remains grave doubt as to its utility in this disease.

Toxicology.—The symptoms of Calabar bean poisoning have all been stated above. The obvious antidote is atropine, which may often succeed; and the other measures are those usually employed to stimulate the circulation and respiration. Unfortunately the antagonism between physostigmine and atropine is not perfect, and Sir Thomas Fraser has shown that in such cases there comes a time when, if the action of the two drugs be summated, death results sooner than from either alone. Thus atropine will save life after three and a half times the fatal dose of physostigmine has been taken, but will hasten the end if four or more times the fatal dose has been ingested. Thus it would be advisable to use the physiological antidote only when the dose of the poison—assuming estimation to be possible—was known to be comparatively small.