Sigma antagonists potentiate opioid analgesia in rats.

In mice, activation of sigma1 receptors antagonizes opioid analgesia. Sigma antagonists potentiate opioid analgesia, implying that the anti-opioid sigma system is tonically active. Co-administration of haloperidol with the mu opioid morphine, the kappa 1 analgesic U50,488H or the kappa 3 agonist naloxone benzoylhydrazone enhances the analgesic activity of all agents. The effect results from sigma receptor blockade since (-)sulpiride, a selective D2 antagonist which does not block sigma receptors, is inactive.