PHARMACOLOGICAL AND AUTORADIOGRAPHIC DISCRIMINATION OF SIGMA AND PHENCYCLIDINE RECEPTOR-BINDING SITES IN BRAIN WITH ( )-[H-3] SKF-10,047, ( )-[H-3]-3-[3-HYDROXYPHENYL]-N-(1-PROPYL)PIPERIDINE AND [H-3] 1-[1-(2-THIENYL)CYCLOHEXYL]PIPERIDINE

Abstract

The benzomorphan opioid, SKF 10,047, is the prototypical agonist for the sigma receptor. In this study, pharmacological and autoradiographic analyses reveal that (+)-[3H]SKF 10,047 labels two sites in brain: a high affinity site resembling the sigma receptor and a second site, labeled with lower affinity by (+)-[3H] SKF 10,047, similar to the phencyclidine (PCP) receptor. The drug specificity of the high affinity site for (+)-[3H]SKF 10,047 resembles that of the putative sigma receptor labeled with (+)-[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine [(+)-[3H]-3-PPP], being potently inhibited by (+)-3-PPP, haloperidol and (+/-)-pentazocine, and demonstrating stereoselectivity for the (+)-isom..