(-)-Pentazocine analgesia in mice: interactions with a sigma receptor system

(-)-Pentazocine is active in the tailflick assay in CD-1 mice, although it shows a biphasic dose-response curve with a peak effect of only 30%. Co-administration of haloperidol shifts the dose-response curve to the left and elevates the maximal response to 70% through a blockade of sigma 1 receptors, but the curve remains biphasic. (+)-Pentazocine is inactive in all antinociceptive assays, either alone or with haloperidol. The analgesic actions of (-)-pentazocine are readily reversed by nor-binaltorphimine, but not by the mu-selective opioid receptor antagonist beta-funaltrexamine, implying a kappa 1-opioid receptor mechanism of action. This conclusion is supported by the ability of antisense oligodeoxynucleotides directed against the KOR-1 clone, which encodes the kappa 1-opioid receptor, to block (-)-pentazocine analgesia.