Curare

Curare. Woorari. Woorara. Woorali. Urari.—This powerful South American arrow poison was first brought to Europe by the celebrated traveller Waterton; it was in the form of a thick syrup, but as it now occurs in commerce it is a blackish extract, brittle, somewhat resinoid in appearance, encrusting the sides of gourds or little rude earthenware jars, into which it has been poured in a liquid state. The drug varies much in strength. It has been variously described. According to the researches of Planchon (P. J., xi, 491), there are really four distinct varieties of curare.

1. That from the Upper Amazon, obtained from the Strychnos Castelnaei Wedd., and possibly from S. Yapurensis G. Planch.
2. That from the Upper Orinoco, extending towards the Rio Negro, yielded by S. Gubleri G. Planch.;this is the variety spoken of by Humboldt.
3. That of British Guiana, obtained from S. toxifera Schomb., associated with S. pedunculata Benth. and S. cogens Benth.
4. That of French Guiana, made out of S. Crevaiuxiana Baill. (S. Crevauxii G. Planch.).

These varieties are, however, commercially indistinguishable. The preparation of woorari has been witnessed by various travellers and variously described. (See P. J., xvi, 502; B. F. M. R., Oct., 1865; P. J., x, 1881.)

The method followed in the Upper Amazon region is to make a decoction of the bark of Strychnos castelnaei, to which one-tenth of the stem of another liane is added. This is then concentrated by evaporation. To this concentrated juice then is added the leaves of Petiveria alliacea, the stems of Dieffenbachia Seguine, the root barks of two plants of the Piperaceae and a species of Marcgravia. The fluid extract is then evaporated until it is in the condition of an extract, and poured into small vessels. Joubert asserts that the Tecuma Indians use, besides S. Castelnaeana Weddell, Cocculus toxiferus and an arum (Taya), which he found to be very poisonous. According to Kobert (Ph. Ztg., June, 1885), Malouetia nitida Spruce (fam. Apocynaceae), or Guachamaca, a plant which is abundant in the Orinoco and Rio Negro districts, enters largely into the composition of curare. The alkaloid, guachamacine, isolated by T. Schiffer in 1883, is very closely allied to, if it be not identical with, curarine, in both its chemical and its physiological activity. It is entirely possible that the varieties of woorari vary in their alkaloid and their physiological properties.

Allied, it may be, to the third variety of woorari are the arrow poisons brought by W. S. W. Ruschenberger from Colombia, and studied by W. A. Hammond and S. Weir Mitchell. (Am. J. M. S., July, 1859.) Corroval was in dark brown lumps, having the appearance of a vegetable extract, and of an intensely bitter and persistent taste. They found its activity to depend upon the presence of a peculiar alkaloid, corrovaline. It resembles curare in that it produces general paralysis without previous spasm, but diners, in paralyzing also the heart. Vao or Bao appears to be a dilute and adulterated form of carroval. It would seem, therefore, that there is a variety of "woorari" used in South America which is more closely allied to strophanthus than to the true curares.

The term "curare" has no specific meaning, but according to Whiteford is simply the Indian word for poison, and it is evident that there are a considerable variety of arrow poisons used in South America under the same name.

In 1898 Boehm classified the curares of the markets as Tubocurare, originating from the Amazon, preserved in hollow bamboo canes, and said to contain about 9 to 11 per cent. of tubocurarine as its poisonous constituent; Gourd curare, derived from Strychnos toxifera, very rarely met with, and having curarine and a second alkaloid soluble in ether for its active principle; Jor curare, obtained from Strychnos castelnaei, also exceedingly rare in the European markets, containing three alkaloids—protocurine, having a feeble curare action; the non-poisonous protocuridine; and protocurarine, which is more actively poisonous than is curarine. (Ph. Ztg., xlii, 41.)

R. Boehm has isolated the two bases, curarine (also called tubocurarine from its source in the curare packed in bamboo tubes), C₁₉H₂₆ON₂, and curine, C₁₉H₁₉O₃N. The free tubocurarine forms an amorphous brown-red mass. Boehm (Ber. d. Chem. Ges., xx, 143) states that curine exists in many specimens of curare; it may also be obtained from the aqueous extract of curare. It is much less poisonous than the accompanying curarine. Curine is a crystalline powder fusing at 161° C. (321.8° F.), slightly soluble in cold water, freely soluble in alcohol, chloroform, and dilute acids. It forms a voluminous white precipitate with meta-phosphoric acid.

Woorari is one of those poisons whose active principle passes through animal membranes with difficulty, and hence when given by the stomach or rectum it acts very slowly, and in some cases elimination may proceed so rapidly that no marked influence is exerted, because not enough of the alkaloid is in the blood at any one time. There is also reason for believing that the alkaloid is destroyed in the liver. When injected into a vein, or introduced by the hypodermic needle or the poisoned arrow into the cellular tissue, it acts with great promptness. The symptoms caused are progressive loss of muscular power, the animal growing weaker and weaker, the respirations becoming more and more feeble, until death by asphyxia results.

The action of curare is to paralyze the peripheral ends of the motor nerves, the muscles, when directly stimulated, retaining their irritability. In mammals, as a result of the paralysis of the phrenic nerves, there is failure of respiration, and consequent death from asphyxia. The heart usually continues beating after cessation of the breathing, only very large doses affecting the arterial pressure directly. If, however, the dose be sufficient, the drug paralyzes the peripheral ganglia, thereby causing a dilation of the blood vessels with consequent fall of pressure, increased rate of the pulse through lack of inhibitory control, loss of irritability in the secretory nerves, and other modifications of functions of less importance. Tillie (A. E. P. P., xxvi) has brought forward evidence to show that there is a primary excitation of the spinal cord which, however, in ordinary poisoning, is masked by paralysis of the motor nerves. The sensory apparatus does not seem to be affected, unless by enormous doses. Glycosuria has been frequently noticed in animals as the result of curare poisoning. According to Morishima (A. E. P. P., 1889, xlii), this is apparently independent of the amount of glycogen in the liver or muscles.

Voisin and Lionville describe two types of poisoning in human beings. In the milder type the pulse is increased in force and frequency, respirations somewhat rapid, the temperature a little elevated, and the urine contains sugar. After larger quantities symptoms begin with severe chill, tremors, small pulse, and early loss of power in the lower extremities, later the cold skin becomes hot, the pulse rapid and full, there is marked reduction of the body temperature, with redness of the skin, and frequently profuse sweating. In non-fatal cases, the paralysis of the extremities rarely lasts for an hour, but the fever may continue for several days.

In cases of poisoning from the injection of woorari, a ligature around the limb between the place of injection and the heart, the free exhibition of diluents and evacuants, and artificial respiration when required, are the measures recommended. (Ed. M. J., 1867, 667.)

According to the experiments of Joseph Tillie, curine has no influence upon the motor nerves, but acts both in the frog and in the mammal upon the heart, belonging physiologically to the digitalis group. Boehm states that the presence of curine in curare can be recognized by the white precipitate made by metaphosphoric acid.

Although curare has in the past been used as an anti-convulsant in tetanus and hydrophobia, it is a remedy of no practical value, because the phrenic nerve is no less susceptible than the other motor nerves of the body, and if given in sufficient doses to control the spasm, will likely lead to fatal asphyxia. According to the elaborate experiments of Du Cazal (A. G. M., Sept., 1869), from one-fourteenth to one-seventh of a grain (0.005-0.01 Gm.) daily were borne by a dog without inconvenience; at the dose of ten milligrammes the characteristic phenomena began to show themselves, but disappeared in a few hours; with fourteen milligrammes the animal perished. For man the doses administered by subcutaneous injection were from one-twelfth to one-third of a grain (0.005-0.02 Gm.) of the crude curare. According to Bernard, curarine is at least twenty times as strong as curare.

The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.