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

In a previous study of curarizing agents in unanesthetized volunteers (1) equipotent doses were established for d-tubocurarine (dTC), dimethyl d-tubo-.curarine (dimdTC) and decamethylene-bis(trimethylammonium bromide) (ClO). For the comparison of potency a 95 per cent decrease in grip strength was chosen as the standard of curarization. Effects of equipotent doses (GD95) of the drugs on respiration were also determined and expressed as per cent decrease in vital-capacity (VCos9s). Furthermore, time for 75 per cent recovery of grip strength (t75) after equipotent doses of the drugs was determined. It was shown that the effects of the drugs were significantly characteristic for each drug. Further sta-tistical investigation of these drug effects has now been made. Curves relating dose and effect on grip strength have been calculated, as well as curves relating-decrease in vital capacity to decrease in grip strength. Analysis and interpolation on these curves provide new information which further characterizes the actions.of these drugs on normal subjects. Previous experiments in which the curarizing agent was administered in a single dose, were extended to repeated administrations at intervals comparable to those used in anesthesia. Two doses of the curarizing agent were given within.a period of less than one hour, in order to obtain further information on the per-#{149}sistenceof the drug in the body, its duration of action and potential cumulative.effects. Reproducibility of response to repeated doses was also studied in experi-ments on intact animals (mice, rabbits, cats)