§ 491. Physiological Action.—The physiological action of physostigmine is strikingly like that of nicotine, which it resembles in being a respiratory poison, first exciting, afterwards paralysing the vagus. Like nicotine, also, it produces a great loss of muscular power; it first excites, and then paralyses the intra-muscular terminations of the nerves; and, again, like nicotine, it induces a tetanus of the intestine. A difference between physostigmine and nicotine exists in the constant convulsive effects of the former, and in the greater influence on the heart of the latter.
§ 492. Post-mortem Appearances.—But little is known relative to the post-mortem appearances likely to be found in human poisoning; redness of the stomach and intestines is probably the chief sign.
§ 493. Separation of Physostigmine.—For the extraction of physostigmine from the fluids of the body, Dragendorff recommends benzene: the alcoholic filtered extract (first acidified) may be agitated with such solvents as petroleum and benzene, in order to remove colouring matter; then alkalised and shaken up with benzene, and the latter allowed to evaporate spontaneously—all the operations being, as before stated, carried on under 40°. If much coloured, it may be purified according to the principles before mentioned. In cases where enough of the extract (or other medicinal preparation) has been taken to destroy life, the analyst, with proper care, would probably not have much difficulty in separating a small quantity of the active principle. It is rapidly eliminated by the saliva and other secretions. In most cases it will be necessary to identify physostigmine by its physiological activity, as well as by its chemical characters. For this purpose a small quantity of the substance should be inserted in the eye of a rabbit; if it contains the alkaloid in question, in twenty minutes, at the very latest, there will be a strong contraction of the pupil, and a congested state of the conjunctival vessels. Further researches may be made with a small quantity on a bird or frog. The chief symptoms observed will be those of paralysis of the respiratory and voluntary muscles, followed by death. If a solution is applied to the web of a frog’s foot, the blood-vessels become dilated. Physostigmine appears, according to Dragendorff and Pander, to act as an irritant, for they always observed gastro-enteritis as a result of the poison, even when injected subcutaneously. The enhanced secretion from all mucous surfaces, and the enlargement of the blood-vessels, are also very constant symptoms. But of all these characteristics, the contraction of the pupil is, for the purposes of identification, the principal. A substance extracted from the tissue or other organic matters, in the manner mentioned, strongly contracting the pupil and giving the bromine reaction, would, in the present state of our knowledge, be indicative of physostigmine, and of that alone.
§ 494. Fatal Dose of Physostigmine.—One mgrm. (·015 grain) as sulphate, given by Vee to a woman subcutaneously, caused vomiting, &c., after half an hour. A disciple of Gubler’s took 2 mgrms. without apparent effect; but another mgrm., a little time after, caused great contraction of the pupil and very serious symptoms, which entirely passed off in four hours. It would thus seem that three times this (i.e., 6 mgrms.) would be likely to be dangerous. If so, man is far more sensitive to physostigmine than dogs or cats; and 3 mgrms. per kilo.—that is, about 205 mgrms. (3 grains)—would be much beyond the least fatal dose.
IX.—Pilocarpine.
§ 495. From the leaves of the jaborandi, Pilocarpus pennatafolius (Nat. Ord. Rutaceæ), two alkaloids have been separated—jaborandi and pilocarpine.
Jaborandi (C10H12N2O3) is a strong base, differing from pilocarpine in its sparing solubility in water, and more ready solubility in ether; its salts are soluble in water and alcohol, but do not crystallise. P. Ghastaing,[541] by treating pilocarpine with a large quantity of nitric acid, obtained nitrate of jaborandi, and operating in the same way with hydrochloric acid, obtained the hydrochlorate of jaborandi; hence, it seems that jaborandi is derived from pilocarpine.
[541] Compt. Rend., vol. xciv. p. 223.