Curara

Woorara

History

There are no official preparations. The substances known under this name vary much in purity, and differ in origin. True curara is a poisonous substance, prepared by the Indian tribes of certain districts of South America, and known under the names woorara, urari, wurali, etc. A specimen examined by Mitchell and Hammond consisted of two distinct preparations named respectively carroval and vao, the former more closely corresponding to the European specimens. Curara is obtained for the most part from several plants of the Strychnos family, as Strychnos toxifera, S. cogens, and from Paulinia cururu. An extract from these plants, it is supposed, is mixed with the venom of certain poisonous reptiles, and possibly with other animal substances. As the arrow-poison of different tribes differs not only in strength, but in the character of the effects produced by them, it is certain that they are derived from different sources. That which is now obtained in commerce as curara, and which agrees in the main with the description of Bernard, is the substance referred to in this article.

Composition

Curara occurs in small, irregular masses, of a dark-brownish color, somewhat slimy, and looking like a dried vegetable extract. The mass is in part soluble in water, and the undissolved residue is composed, for the most part, of starch-granules, vegetable cells, oil-drops, and other vegetable structures (Mitchell and Hammond). The existence of an alkaloid in curara had been suspected by Boussingault, but it was not actually discovered until 1865, when it was isolated by Preyer (curarine). The estimates formed of its activity vary: by Preyer it was held to be twenty times stronger than the crude drug, but by Beigel only six times; but these differences are readily accounted for in the varying qualities and activity of curara.

Curarine, one of the alkaloids, is crystallizable, deliquescent, and forms with acids salts, which are also crystallizable. The dose will range from 1/100 gr. to 1/40 gr. by the stomach—from 1/200 gr. to 1/100 gr. when administered subcutaneously. A larger quantity may be necessary when distinct physiological effects are to be produced.

Another alkaloid has since been discovered by Böhm, and to this he has assigned the name curine.

The dose of woorara or curara, the crude drug, will range from 1/20 gr. to 1/5 gr. It is desirable to try on some inferior animal the activity of any new specimen before using it on man.

Antagonists and Incompatibles

As curara is a paralyzer, it is antagonized by those agents which act in the opposite manner on the spinal cord. From the physiological standpoint, strychnine and atropine are appropriate antagonists, opposing the tendency to death by failure of respiration. Remarkable results have been obtained in animals by artificial respiration. An animal will recover from twice the fatal quantity, if respiration be kept up until elimination occurs, which is speedy. As in the case of the other alkaloids, curarine is destroyed by the caustic alkalies.

Synergists

The paralyzers in general, especially the respiratory group, promote all of the actions of curara.

Physiological Actions

The taste of curara is bitter. Applied to the unbroken integument, it is not absorbed; but swallowed, it slowly diffuses into the blood, and produces characteristic effects. Vulpian finds that it is absorbed more rapidly when injected into muscular masses than when simply thrown under the skin. According to the observations of Voisin and Liouville, made on man, the salivary, nasal, and lachrymal secretions are increased. It is probable that the gastrointestinal secretions are also promoted. The rate of diffusion into the veins from the stomach varies, but it takes place in from twenty minutes to a half-hour; but even a longer time than this may be required. The action of the heart increases; the pulse rises a number of beats and may be dicrotic; the temperature ascends two to three and a half degrees, and the respirations are accelerated, four to eight times per minute being added to the usual rate. Voisin and Liouville ventured on the exhibition of larger doses with the following result: the symptoms began by a more or less violent chill; the heart beat rapidly, reaching 140, and the pulse became weak; the respiration was labored and sighing; the temperature rose, and double vision, sometimes with mydriasis, sometimes with myosis, set in. The legs became weak, coordination was destroyed, and the vertical position could not be maintained. The mind continued undisturbed. The paralysis disappeared after a short time, but a sense of fatigue persisted in the limbs for some hours. The increased temperature was accompanied by the usual symptoms of fever—there were, besides the accelerated pulse and respiration, headache, thirst, and perspiration.

It was by means of curara that Bernard demonstrated the existence of contractility as an independent endowment of muscular tissue. Curara, by poisoning the end-organs of the nerves in the muscles, separated these organs, and thus permitted a study of the agency of each. In all classes of animals, as in man, curara induces paralysis of movements: locomotion, the erect posture, breathing, finally the heart's action, are arrested. The paralysis induced by curara is not due to an abolition of the excitability proper to the motor nerve-trunks, but to a modification set up in the terminals of the intra-muscular nerves. This fact is proved by the well-known experiment of Bernard, repeated by Kölliker, Zeleuski, Vulpian, and numerous other experimentalists, in which a frog is paralyzed by curara in all parts of the body except one limb which has been ligatured to prevent the access of the poison to it. The muscles of the unpoisoned limb react normally to stimulation, to the will, and to reflex impressions from distant parts. The muscles of the poisoned parts of the body act on direct stimulation, but not by the will nor by any direct or reflex excitation conveyed by the nerve. The paralysis must therefore be due, as above stated, to the effect of the poison on the terminals of the nerve in the muscular tissue. As movements can be induced in the muscles of the unpoisoned limb by irritation of the skin at a distant point, it is clear that the sensory nerves and the reflex function of the spinal cord continue active. It has been abundantly demonstrated that in curarized animals the spinal cord preserves its functions for a long time. If, however, a large quantity of the poison is administered, and a fatal result prevented by artificial respiration, the excitability of the cord is at first increased but afterward paralyzed (Von Bezold, Vulpian, etc.). The motor and sensory nerve-trunks are also finally affected, but this is a secondary action, and ascertainable in curarized animals only by maintaining artificial respiration a sufficient length of time. It follows, then, that all parts of the nervous system are ultimately paralyzed. The action begins in the end-organs of the motor nerves, and then gradually extends to all parts, if the dose is large enough and life is maintained by artificial respiration.

Curara also acts on the accelerator nerves of the heart, at first stimulating and afterward paralyzing them. The action of the heart is increased, also, by the paralyzing effect of curara on the terminals of the pneumogastric, thus removing the inhibition. So decidedly is the vagus affected by full doses of curara, that galvanic irritation does not arrest the movements of the heart (Von Bezold). Notwithstanding the increased action of the heart, the blood-pressure is lowered by curara, due doubtless to a paralyzing action on the organic muscular fiber and consequent dilatation of the vessels. The effect of curara on the sympathetic is variously interpreted. According to Vulpian, the iris contracts on changes in the amount of light falling on the retina in curarized animals; the pupils dilate on faradization of the skin; dilatation of the vessels of the posterior members and an elevation of temperature take place in a curarized dog on faradizing the central portion of the corresponding sciatic; very energetic reflex contractions of the stomach, intestines, and bladder are obtained in curarized animals by faradizing the skin of different regions of the body (Vulpian). These facts indicate that curara does not destroy but rather stimulates the functions of the sympathetic. Curara acts on the lymph-vessels of frogs. According to Tarchanoff, the liquid which accumulates during curarization grows richer in leucocytes; also the blood contained in the vessels becomes more concentrated, the relative proportion of red globules being increased. As the accumulation of leucocytes takes place in the lymph-sacs, there is a corresponding diminution of them in the blood. These changes are due to the paralysis of the peripheric vessels (Tarchanoff)