BLOCKADE OF THE ANTINOCICEPTIVE ACTIVITY OF CENTRALLY ADMINISTERED KETOROLAC BY NOR-BINALTORPHIMINE

Antinociceptive activity of intracerebroventricularly administered ket orolac tromethamine was evaluated in mice by measuring inhibition of a bdominal stretching induced by p-phenylquinone. Ketorolac tromethamine produced dose-dependent antinociception with an ED(50) of 7.34 mu g/m ouse (4.97-10.82) and a maximal effect at 30 mu g. Selective antagonis ts of opioid receptors were used to determine ketorolac's mechanism of action. The ketorolac tromethamine-induced antinociception was not bl ocked by the mu- and delta-opioid receptor antagonists, naloxone and I CI-174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu), respectively; however, t he kappa-opioid receptor antagonist nor-binaltorphimine dihydrochlorid e significantly blocked this effect. These findings suggest that activ ation of kappa-opioid receptors appears to play a role in the mechanis m of the antinociceptive effect of ketorolac tromethamine. Ketorolac t romethamine may induce the release of endogenous -opioids to produce c entral nervous system antinociception.