Curare: the South American arrow poison.

The history of curare is both curious and convoluted. A product of South American culture it emerged in the sixteenth century from the mists of antiquity at the same time as quinine, coca, and chocolate. Like quinine, at first came the extract but no plant, and later the plant but no chemical compound. It took more than 300 years and the efforts of many explorers and scientists to resolve the problem. These included Condamine, Humboldt, Brodie, Waterton, Bernard, Dale, Walker, and King. Finally, the pure compound d-tubocurarine was isolated from the liana Chondrodendron and synthesised. Its specific physiological action was blockade of the effect of acetylcholine at the neuro-muscular junction. Such a paralytic poison could be used to kill oneself or others. The bizarre plot to kill the Prime Minister, Lloyd George, during the First World War is described. Fortunately this nefarious plan was thwarted by the Secret Service!

Ethnopharmacology in drug discovery: an analysis of its role and potential contribution.

In this paper we discuss some examples of ethnopharmacological research as it has been conducted during the last two centuries and look at the current role of this discipline in drug discovery (especially with respect to the American and European markets) and the further development of these phytotherapeutical resources for local use in the countries of origin (ethnopharmacology). Examples from 19th century research on curare (Humboldt and Bernard), from the 20th century on hallucinogenic mushrooms (Wasson), on Mexican Indian indigenous plants (our own research) and of current industry based research are used to illustrate the development of this discipline and to highlight the challenges for the future.

[A new toy: upswing in curare use in Spanish anesthesia]. / A new toy: la irrupción del curare en la anestesia española (1946).

The introduction of curare for general anesthesia by Harold Griffith in 1942 was one of the most important moments in the development of anesthesiology. However, several years passed before curare came to be used in Spain. We review the early application of curare and the role played by Robert Macintosh, Professor of Anaesthesia at Oxford, in introducing the drug to Spain.

Direct negative chronotropic and inotropic efects of curare on isolated and perfused frog's heart

It has been stated that curare has no direct effect upon the heart because the cardiac muscle is deprived of nicotine receptors. While performing an experimental work, we noticed that when high doses of curare were administered to frogs, a change in cardiac activity occurred. In order to elucidate whether the cardiac effects of curare wee the results of a direct action or a reflex response, we studie the effects of increasing doses of d-tubocurarine on the rate and contractility of 8 isolated and perfused frogs'hearts. After testing the d-tubocurarine effects on the heart rate and contractility, we added either acetylcholine, atropine, atenonol or verapamil in orden to find out whether any change ocurred in the cardiac effects produced byd-tubocurarine. Thirty seven measurements were carriet out and it wasfound that 1) high doses (between 1 and 15 micrograms) of d-tubocurarine produced a highly significant decrease in heart rate an contractility; 2) d-tubocurarine did not avoid the acetycholine effect; 3) atropine, atenonol and verapamil did not interfere with d-tubocurarine effects. We conclude that high doses of d-tubocurarine produce "dosis-dependent" heart rate and contratility reductions. These effects are not mediated by muscarinic receptors beta-1 receptors or the show calcium channels

Some clinical evidence for a quantitative relationship between dose of relaxant and plasma protein

A study of curare requirement for routine surgery on Jamaican patients demonstrated the possible existence of a group of refractory subjects. Further clinical studies of curare and other relaxants were made to acertain whether this tolerance is associated with the high serum globulin found in this community. A correlation between dose and serum globulin was found to be significant for gallamine triethiodide and nearly significant for decamethonium iodide and d-tubocurarine chloride. Correlations of dose of d-tubocurarine and gallamine with serum gamma-globulin were less significant than with total globulin (AU)