Anti-opioid activity of sigma 1 systems

Abstract

(+)Pentazocine is a potent sigma 1 ligand which antagonizes mu, kappa 1, kappa 3 and delta analgesia. This antagonism is reversed by haloperidol, which blocks both D 2 and sigma receptors, but not by sulpiride, a selective D 2 drug without sigma activity. Haloperidol (< 1 mg/kg) shifts the dose-response curves for morphine in CD-1 mice approximately 2-fold and is more effective against kappa analgesics. These shifts argue for a tonic activity of this anti-opioid system. This anti-opioid system also contributes to the differences in opioid sensitivity among strains of mice.