FUNCTIONAL ANTAGONISM OF MORPHINE ANALGESIA BY (+)-PENTAZOCINE - EVIDENCE FOR AN ANTI-OPIOID SIGMA(1) SYSTEM

Both (+)-pentazocine and ( - )-pentazocine antagonize morphine analgesia equally well. This lack of stereospecificity implies an non-opioid mechanism of action. The antagonism of morphine analgesia by ( + )-pentazocine is reversed by haloperidol, a potent dopamine D2 and sigma receptor antagonist. The inactivity of the highly selective dopamine D2 receptor antagonist (-)-sulpiride indicates that both (+)-pentazocine and haloperidol arc acting through sigma receptors. Haloperidol, but not (-)-sulpiride, also enhances morphine analgesia. Together, these results suggest the presence of a tonically active anti-opioid sigma system within the brain.