EVALUATION OF CURARIZING DRUGS IN MAN

II. Analysis of Response Curves and Effects of Repeated Administration of D-Tubocurarine, Dimethyl-D-Tubocurarine and Decamethylene-Bis(Trimethylammonium Bromide)

¹ Departments of Pharmacology and Surgery (Anesthesia), University of Illinois, College of Medicine, Chicago 12, Illinois

1 . Effects of curarizing agents in depressing vital capacity relative to depressing grip strength were dependent on the threshold of the respiratory musculature to the drug in question. Curarization, once begun, proceeded at an equal rate in the muscles of respiration and hand grip.

2. No "respiration sparing" effect of C10 was observed in man. In equipotent doses, C10 depressed vital capacity most profoundly, while dimdTC had the least effect on respiration. The "coefficient of safety" was lowest for C10, highest for dimdTC.

3. dTC and dimdTC persisted in the body after recovery of grip strength had occurred; 45 minutes after administration of a standard dose, half that dose produced effects comparable to those of the standard.

4. Tachyphylaxis to the curarizing effects of C10 was observed in man; 30 minutes after administration of a standard dose, a second injection of the same dose failed to cause an equal degree of paralysis. Tachyphylaxis to C10 could not be demonstrated in animals.

5. Marked species variation in responses to curarizing drugs was encountered. Prediction of quantitative responses in man, on the basis of experiments performed in animals, is fraught with danger.