The poisonous preparation, Curare.
Source and History.—Curare is a frightfully poisonous extract, prepared by the savages of South America, for the purpose of poisoning the points of their arrows. It is known under various names, bearing a general resemblance, such as woorari, woorara, curari, cururu, ourari, wourali, etc. It is said to have been first brought to Europe by Sir Walter Raleigh. It was mentioned by the Fathers d'Acunja and d'Artieda, who visited the Amazon River in 1693 (New Remedies, 1877). In 1745, De la Condamine brought the poison to the notice of the French Academy. It was carefully described by Waterton (1812) (Waterton's Wanderings in South America), together with a process of preparation, as followed by the Macoushi Indians.
Regarding its origin authorities disagree, but it is known that different tribes vary the plants that enter into its composition, and thus we have little reason to doubt the conflicting statements of travelers. Waterton states that a vine called by the Macoushi Indians "Wourali," is the poisonous agent; although, according to him, they add the fangs of vipers, and plants that simply give bulk to the extract. Bancroft (1769) obtained from the Accawan Indians, a receipt for making it from native plants, under local names, and from one of these plants (woorara) the extract seemed to derive its name. According to a more recent authority, Dr. Jobert, the Tecuna Indians, at Calderao (Brazil), prepare curare from Strychnos Castelnaei, Weddell, Cocculus toxiferus, Weddell, Didelphys cancrivora, a plant belonging to the Arum family, known as "Taja," a plant of local name "Toucan's tongue," and three Piperaceae of the genus Artanthe. These are extracted with water, and evaporated to an extract. According to Jobert, the Strychnos Castelnaei and the Taja are the most poisonous of the constituents (New Remedies, April, 1878, from Bulletin de Therapeutique). M. Planchon, in 1888 (Jour. de Pharm. et de Chim., p. 539), summarizing what was known regarding the botanical origin of the various kinds of curare, states that the curare of the Amazon is derived from Strychnos Castelnaeiana, Baillon (S. Castelnaei, Weddell); that of British Guiana from Strychnos toxifera, and that of French Guiana from Strychnos Crevauxii (named by Planchon). The curare of the Orinoco region, according to Gaillard's report, is of two kinds; one of weaker activity, from Strychnos Gubleri, used for hunting purposes, and another (strong curare) from Strychnos toxifera, a plant that extends over a vast territory in South America.
Description and Chemical Composition.—In appearance curare seems to differ according to its origin and its age. Sometimes it is described as a syrup, into which the points of the arrows are dipped; again, it is of a hard, resinous appearance. It is, in reality, simply a vegetable extract, and may be expected to vary as much as other extracts; and we know that time and mode of preparation will change the general appearance of all solid extracts. In quality also, it is uncertain; according to Blodgett (1878), the most active article presented a glistening fracture, and was of a dark-brown color. Doubtless, those specimens which contain the largest proportion of the extract from the species of Strychnos, or of Cocculus toxiferus, are most poisonous. Although, in 1828, Roulin and Boussingault announced the poisonous principle to be curarine, yet, for some years afterward, it was erroneously believed by many that curare depended upon strychnine and brucine for its poisonous property, for Oberdörffer had announced that woorara, from three sources, yielded both strychnine and brucine, and Wittstein stated that both alkaloids are present in woorara from Brazil, and in the wood of Strychnos toxifera, Schomburghk. It is generally accepted, at the present day, that curare contains curarine, a very poisonous substance, resembling strychnine in some respects, but differing quite markedly in others.
Curare is of a bitter taste, soluble in cold water to the extent of about 75 per cent, which fluid also extracts the poisonous substance known as curarine. Curarine (C18H35N) (Sachs) is an alkaloid, and was discovered by Roulin and Boussingault. It is colorless or white, of a bitter taste, deliquescent to a certain extent in moist air, soluble in water, and in alcohol, less soluble in chloroform, and insoluble in pure ether, benzol, oil of turpentine, and disulphide of carbon. It has an alkaline reaction, and unites with acids to form crystallizable salts. According to Sachs, it exists naturally as a sulphate. It may be separated from strychnine, if mixed with that alkaloid, by benzin, in which substance, according to Flückiger, curarine is insoluble. According to R. Böhm (1887) curarine is yellow and neutral in reaction. Its aqueous solution is fluorescent (greenish) and when evaporated, after the addition of a mineral acid, yields non-toxic, acicular crystals. Curare when treated with water, leaves from 5 to 50 per cent of a residue; the solution contains large amounts of another alkaloid of a non-poisonous character, soluble in diluted sulphuric acid, and named by Böhm curine. By treatment with iodide of methyl, curine yields an alkaloidal body exhibiting the poisonous activity of curare itself. Curine is amorphous, but may be crystallized from ethereal solutions. It is little soluble in water, but easily soluble in alcohol (Jahresber. der Pharm, 1887, p. 415).
Action, Medical Uses, and Dosage.—Curare, or woorara, produces its poisonous effects only when it has penetrated into the circulation, either by means of a wound, by rectal injection, or by inhalation (Pelouze and Bernard). When applied to the skin it powerfully irritates. It first paralyzes the voluntary and then the involuntary muscles, death, when it occurs, being due to respiratory paralysis. It is seldom toxic when introduced into the stomach, although it would be prudent to use some care in its internal administration, as fatal results are stated to have followed its ingestion in maximum doses, or when taken upon an empty stomach. However, saccharine urine and profuse perspiration are said to have been produced by its internal administration. The symptoms following its introduction into the circulation are muscular paralysis (which, more or less rapidly, becomes general), stupor, suspended respiration, sometimes convulsions, and death, the heart continuing to act for some time after all other indications of life have disappeared. It is stated that animals have recovered from its effects, even at this stage, artificial respiration having been resorted to before the heart had wholly ceased its action. The difference in the character, and in the rapidity of the symptoms observed in poisoning by this agent, is supposed to be due to a difference in its composition, and to its more or less rapid expulsion through the urinary organs. The causes of the phenomena produced by it are not satisfactorily determined; they have been variously attributed to paralysis of the respiratory nerve centers, and of the motor nerves; to a primary and direct action upon the heart; to a primary influence upon the nerve terminations, etc. It has no effect upon the pulse or physical temperature, and no perceptible change has been observed in the character of the blood nor in that of the solid textures; hence it can not be a blood poison.
Vella (Pharm. Jour., 2d series, Vol. II), in 1861, decided that strychnine and the poisonous principle of curare, antidoted each other, basing his assertions upon actual experiments, in which large doses of both substances were administered to dogs without fatal effect, while afterward the same amount of strychnine alone, resulted in death, but caution must certainly be observed in the use of so powerful a poison, even in the way of an antidote. In the N. Y. Med. Gaz., July, 1855, Drs. Brainard and Green announced that a solution of iodine 1 part, iodide of potassium 2 parts, and water 48 parts, acts as an antidote to the poison when the antidote is injected under the skin, and neutralizes it when mixed with its solution. Extreme care must be employed both in handling and administering so deadly a substance. It should by no means be permitted to come into contact with a cut, abrasion, or scratch; indeed, it were safer never to handle it with the naked fingers; neither should we attempt to pulverize the dry article, as its inhalation is dangerous. Mr. H. S. Wellcome exhibited, at the meeting of the American Pharmaceutical Association, held in Indianapolis, Ind., 1879, arrows brought by himself from South America and poisoned by the Indians with curare. These arrows bad been dipped into a paste (soft extract), about 1/2 an inch of each point being covered with the poisonous extract. Mr. Wellcome informed Prof. Lloyd that the natives could antidote the poison if treatment was instituted at once, but that they refused to name the antidote.
The therapeutical employment of curare has been suggested in certain severe and obstinate spasmodic affections, as in epilepsy, chorea, hydrophobia, and, more particularly, in tetanus. It is used by subcutaneous injections of its filtered aqueous solution, thus: Add curare 1 grain, to distilled water 24 minims; dissolve, let the solution stand 48 hours, and filter; of this, from 2 minims (1/12 grain) to 6 minims (1/4 grain) may be used at one injection, carefully repeating the injections until relaxation of the muscles has been effected. Curarine, dissolved in water, with a few drops of sulphuric acid added, to facilitate its solution, is to be used in still smaller doses—from the 1/240 to the 1/120 part of a grain. It is doubtful whether this agent will ever come into general use as a medicinal remedy; at least, not so long as other medicines are known in which greater confidence can be placed. The diversity of action, attributable, in some instances, to its difference of composition, in others to its inertness, or to its highly active qualities, render it an uncertain, as well as an unsafe, remedy.
Related Substances.—Musculus venenosus, Mussel.—Owing to the presence probably of certain ptomaines, some mussels are poisonous, or, at least, edible mussels may become occasionally toxic, as, when kept in filthy water, abounding in amoeba, bacteria, etc. Brieger has shown that one of these animal bases (mytilotoxine, C6H15NO2) has physiological actions similar to curare. Mussels are rendered non-toxic by being boiled in weak alkaline solutions. (For an interesting account of this subject, see, Vaughan and Novy's Ptomaines, etc., 1896).
CHINOTOXINE, or Dichinolindimethylsulphate.—A new synthetic product is reputed to act like curare.