Abstract

Nalorphine and (-)-3-hydroxy-N-propargylmorphinan (NIH 6045), two effective narcotic antagonists, were given intravenously in cumulative doses of 1.0 mg/kg as a supplement to thiopental-nitrous oxide anesthesia. Both compounds failed to produce the severe respiratory depression seen after morphine given in this manner and dose. In a complete crossover study of five normal volunteers, 10 mg of nalorphine intramuscularly depressed respiration to the same degree as 10 mg of morphine. In an incomplete crossover study in the same subjects, a cumulative dose of 1.0 mg/kg of nalorphine intravenously failed to produce dose-related respiratory depression, and the degree of depression was much less than that produced by a smaller dose of morphine. In contrast to morphine, nalorphine increased the slope of the respiratory stimulus-response curve. It was concluded that while both drugs are respiratory depressants in man, the ceiling effect for respiratory depression by nalorphine is considerably less than that of morphine. The implications of these observations were discussed.