pain though they were not able to do anything about it since they were essentially paralyzed. On January 23, 1942, Harold Griffith and Enid Johnson gave a synthetic preparation of curare (Intercostrin/Intocostrin) to a patient undergoing an appendectomy (to supplement conventional anesthesia). Safer curare derivatives, such as rocuronium and pancuronium, have superseded d-tubocurarine for anesthesia during surgery. When used with halothane d-tubocurarine can cause a profound fall in blood pressure in some patients as both the drugs are ganglion blockers. However, it is safer to use d-tubocurarine with ether. In 1954, an article was published by Beecher and Todd suggesting that the use of muscle relaxants (drugs similar to curare) increased death due to anesthesia nearly sixfold. This was refuted in 1956. Modern anesthetists have at their disposal a variety of muscle relaxants for use in anesthesia. The ability to produce muscle relaxation irrespective of sedation has permitted anesthetists to adjust the two effects independently and on the fly to ensure that their patients are safely unconscious and sufficiently relaxed to permit surgery. The use of neuromuscular blocking drugs carries with it the risk of anesthesia awareness. Plant sources There are dozens of plants from which isoquinoline and indole alkaloids with curarizing effects can be isolated, and which were utilized by indigenous tribes of Central and South America for the production of arrow poisons. Among them are: In family Menispermaceae: Genus Chondrodendron notably C. tomentosum Genus Curarea, species C. toxicofera and C. tecunarum Genus Sciadotenia toxifera Genus Telitoxicum Genus Abuta Genus Caryomene Genus Anomospermum Genus Orthomene Genus Cissampelos, section L. (Cocculeae) of genus Other families: several species of the genus Strychnos of family Loganiaceae including S. toxifera, S. guianensis, S. castelnaei, S. usambarensis a plant in the subfamily Aroideae of family Araceae called taja at least three members of the genus Artanthe of family Piperaceae Paullinia cururu in the family Sapindaceae Some plants in the family Aristolochiaceae have also been reported as sources. Alkaloids with curare-like activity are present in plants of the fabaceous genus Erythrina''. Toxicity The toxicity of curare alkaloids in humans has not been established. Administration must be parenterally, as gastro-intestinal absorption is ineffective. LD50 (mg/kg) human: 0.735 est. (form and method of administration not indicated) mouse: pot: 0.8–25; tubo: 5-10; calabash: 2–15. Preparation In 1807, Alexander von Humboldt provided the first eye-witness account of curare preparation. A mixture of young bark scrapings of the Strychnos plant,