Naloxone blockade of morphine analgesia: a dose-effect study of duration and magnitude

R Markowitz, J Jacobson, G Bain and C Kornetsky

The purpose of the experiment was to determine the minimal dose of naloxone needed to block the analgesic effect of morphine as measured by the foot-shock titration procedure in the rat. Various groups of rats received, subcutaneously, various doses of naloxone hydrochloride, from 0.03 to 2.0 mg/kg, 15 minutes before receiving 10 mg/kg of morphine sulfate. The results indicate that 1.0 mg/kg of naloxone is the minimum dose necessary to provide full blockade of the measured morphine effect for up to 5 hours after the morphine administration. Partial blockade was evident at doses much smaller than 1.0 mg/kg of naloxone. A dose of 0.125 mg/kg of naloxone completely blocked the onset of a measurable effect from 10 mg/kg of morphine for 60 minutes in six out of the seven animals tested at that dose. The results provide a clear dose-effect relationship for both magnitude and duration of naloxone blockade of the analgesic effect of morphine.

Volume 199, Issue 2, pp. 385-388, 11/01/1976
Copyright © 1976 by American Society for Pharmacology and Experimental Therapeutics