Interactions of narcotic antagonists and antagonist-analgesics

Abstract

In the rat the potent narcotic antagonist N-cyclopropylmethyl-6,14-endoethano-7α- (1-hydroxy-1-methylethyl)-tetrahydronororipavine (M5050, Reckitt), which itself lacks analgesic activity, resembled naloxone in its capacity to reverse the antinociceptive effects of morphine antagonist-analgesics. The nociceptive stimulus employed was bradykinin administered by an intra-arterial route. ED50 values were established for the reversal by M5050 of the analgesic effect of nalorphine, levallorphan, pentazocine and some newer compounds. When antagonist-analgesics were given concomitantly with morphine the response varied from antagonism of the analgesic effect of the morphine to synergism, depending on the dose combination.