This section is from the book "Materia Medica And Therapeutics - Vegetable Kingdom", by Charles D. F. Phillips. Also available from Amazon: Materia Medica And Therapeutics: Vegetable Kingdom.
Description. - Curara, as seen in England, is a blackish-brown substance, of consistency varying from that of an extract to a resin. The taste is very bitter. It is readily soluble in water, and when heated gives out an odor resembling that of chocolate. The physiological action is highly characteristic, and serves at once for the identification of this curious drug. If the smallest possible drop of the solution be injected beneath the skin of a frog, the animal immediately becomes paralyzed in all its voluntary muscles.
Active Ingredients. - The whole activity of curara has been satisfactorily proved to depend upon the presence of the alkaloid cura-rine, discovered by Roulin and Boussingault in 1830, and procured in well-defined crystals by Preyer in 1865. These crystals are four-sided, colorless prisms, of very bitter taste, and having a weak alkaline reaction. They readily attract moisture, are very soluble in water and in alcohol, but not at all soluble in pure ether, sulphide of carbon, benzol, or turpentine. No chemical formula can at present be safely given.
Physiological Action. - Curara induces a very marked and peculiar effect upon the system, and exactly the same follows the use of its alkaloid curarine, only that the intensity of the action of the alkaloid is far greater. The course of the symptoms is the same in mammalia as in frogs; the limbs are first paralyzed, the respiratory muscles then rapidly lose power, and the breathing becomes slower and slower, until at last it ceases entirely. The circulation is at first quickened, the heart acts no longer; and as death comes on, there occurs a flow of saliva and of tears. Slightly convulsive movements are likewise perceived in the first stage of certain cases. In mammalia this remarkable action of curara can be set aside by prompt resort to artificial respiration. In fact, it is now a constant practice with experimenters to curarize animals, and to establish artificial respiration, as a preliminary to physiological experiments which require absolute stillness. Under the influence of the restored respiration (if the dose be not too large) the heart resumes and maintains its action, although the paralysis of the limbs persists. If a rather considerable dose be injected into the jugular veins, the blood-pressure in the systemic arteries becomes greatly lowered, and the pulse-frequency is much increased. Later on, both of these conditions disappear. The intestinal movements are greatly accelerated, and there is also a much heightened sensibility of the intestines to stimuli - circumstances which present a marked contrast to the absolutely paralyzed condition of the voluntary muscular system. A singular feature is the occurrence of decided diabetes, which usually sets in very soon after the injection. The mode of administration exerts a marked influence upon the activity of curara: injection into the jugular vein produces the most powerful effects of all; injection into the subcutaneous tissues comes next; after that comes injection into the lungs; while the stomach absorbs curara so very slowly, that the poison has no time to accumulate in the system, being eliminated with equal rapidity by the kidneys; and, consequently, none of the usual effects are produced on the nervous system. Curarine, in fact, is perhaps more rapidly and completely eliminated than any other alkaloid. Poisoning, it is said, can be induced even by gastric administration of curara if the kidney-elimination be stopped: this was effected in the experiments made by Hermann upon rabbits; his method being to ligature the renal arteries, and then inject curara into the stomach. The effects, however, were anomalous: some of the animals died in convulsions - a very uncommon mode of action for curara; while in others the convulsions were quickly stopped by artifical respiration: they appear to have been due to suffocation from sudden paralysis of the respiratory nerves.
To give a complete account of the physiological action of curara is not possible; but certain facts are clear. It operates in no degree upon the spinal cord; it affects the brain only in an indirect manner. The weight of its operation evidently falls upon the motor nerves: the action commencing towards the periphery, and extending a greater or less distance along their trunks. The muscular substance itself remains unaffected: thus, if the motor-nerve trunks of a curarized animal be Faradized, there is no movement whatever, but direct electrization of the muscles makes them contract quite actively. The vaso-motor nerves appear to be paralyzed: in all probability the increased flux of secretions, and also the cu-rara-diabetes, are due to this paralysis. At a later stage, the pneumogas-tric branches to the heart and to the stomach are disabled, as are also the sympathetic branches to the iris and the vesical nerves; last of all (often after a considerable interval), the musculo-motor cardiac nerves are affected. As regards the sensory nerves, the general opinion has been that curara does not influence them in the least; but the contrary view has been adopted by v. Bezold, and again of late by Lange, who thinks that the sensory nerves are powerfully affected, and that the reflex function of the cord is also impaired.
It has already been mentioned that curara is absorbed only by very slow degrees when introduced into the stomach. It appears from the researches of Claude Bernard and Preyer that curarine shares this peculiarity; its activity when given by the stomach is trifling in comparison with that which it shows when subcutaneously injected, especially when thrown into a vein. The fact of its elimination by the urine was most distinctly shown by Voisin and Lionville, who injected the urine of curarized frogs into healthy frogs, producing the characteristic curara effects; and the matter was carried still further by Bidder, who paralyzed a third frog with urine taken from one that had itself been poisoned by the urine of the animal to which the original dose of curarine had been given. There is no reason, however, to think that the whole of the curarine is eliminated without change: for curarine is known to be exceedingly sensitive to ozone, which destroys its poisonous properties; and it can hardly be doubted that a certain amount of it always gets oxidized and destroyed in the body.