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 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.
Chien
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CC
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pasternak
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GW
D000698:Analgesia; D000818:Animals; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D010423:Pentazocine / Q000494:pharmacology*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology
D065127:Dopamine D2 Receptor Antagonists; D017480:Receptors, sigma; D009020:Morphine; D013469:Sulpiride; D006220:Haloperidol; D010423:Pentazocine