Chien C C, Pasternak G W
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Eur J Pharmacol. 1993 Nov 30;250(1):R7-8. doi: 10.1016/0014-2999(93)90650-7.
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 are 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.
