Potency, duration of action and pA2 in man of intravenous naloxone measured by reversal of morphine-depressed respiration

RD Kaufman, ML Gabathuler and JW Bellville

Placebo and morphine (5 and 10 mg) alone and in combination with naloxone (0.2, 0.4 and 0.8 mg) were administered i.v. to six volunteers. Respiratory responses curves obtained by the rebreathing method were obtained before and 15, 30, 45, 60, 90, 120, 180 and 240 min after the drug infusions. At each time, morphine dose-effect curves, alone and with naloxone, were constructed. Dose ratios and thus the apparent pA2 of these drugs were determined from these curves. The pA2 ia a measure of the affinity of an antagonist for its receptor. The peak effects of both morphine and naloxone occurred at 0.5 hr. Morphine effect showed no significant fall up to 4 hr after infusion. The duration of naloxone appears to be dose-related, statistically significant up to approximately 1.5 hr. The apparent pA2 at each time was calculated by three methods; these values were used, in turn, to calculate the pA2 by a time-dependent method. The apparent pA2 and T1/2 of naloxone in man were determined to be approximately 8.37 and 0.32 hr, respectively. A clinical measure of naloxone potency, the cA2, is proposed.

Volume 219, Issue 1, pp. 156-162, 10/01/1981
Copyright © 1981 by American Society for Pharmacology and Experimental Therapeutics