Pharmacological Studies of d-Tubocurarine and Other Curare Fractions

1. The head drop assay for curare potency is described in detail. The head drop dose falls within the range of 0.125 to 0.175 mg./kg. d-tubocurarine for the rabbit. 2. The toxicity in other species indicates that rats and guinea pigs are more sensitive, having an HD 50 of 0.075 and 0.035 mg/kg. respectively. 3. Neostigmine is a limited antagonist of curare since its is effective against just paralytic doses of d-tubocurarine but is ineffective against higher doses. 4. No change from normal in the degree of paralysis or duration of action of d-tubocurarine was noted in nephrectomized or hepatectomized rats and rabbits. This supports the view that the rest of the body can cope with paralytic doses of d-tubocurarine. 5. With minimum paralytic doses there is no change in blood pressure. As respiration fails the blood pressure falls. High doses cause a vasomotor collapse similar to shock; pressor drugs are partly effective against this vaso-depression. 6. EKG records of cats, dogs, and rats indicate no marked change in rate or in the P-QRST complex with large doses of d-tubocurarine. The relatively low cardiotoxic properties of d-tubocurarine were also ascertained in Straub and Langendorf heart preparations. 7. The EEG in unanesthetized rats, rabbits, and cats remained unchanged with 5 to 50 times the paralytic dose of curare given IV. No signs of central stimulation or depression were seen. 8. When curare is given intracisternally to rabbits it produces violent convulsions with doses of 0.1 mg./kg. 9. The importance of adequate positive artificial respiration preferably with the addition of oxygen, to eliminate effects due to anoxia is emphasized. 10. The possible clinical implications of these studies are discussed.