[H-3]-(-PENTAZOCINE BINDING TO SIGMA-RECOGNITION SITES IN HUMAN 12REBELLUM())

The binding characteristics of the sigma-1 selective benzomorphan [H-3 ]-(+)-penrazocine were determined in human cerebellar membranes. Satur ation binding analysis revealed two affinity sites with a K-DH of 1.4 +/- 0.7 nM and a K-DL of 33.6 +/- 11.9 nM. Kinetic studies performed a t 25 degrees C demonstrated reversible binding with association and di ssociation rate constants determined for two classes of sites. In satu ration binding studies, the addition of (+)-SKF 10,047 occluded bindin g of [H-3]-(+)-pentazocine to high affinity sigma binding sites. The a ffinity profile of ligands displacing [H-3]-(+)-pentazocine was consis tent with the labeling of sigma-1 recognition sites with haloperidol > (+)-pentazocine > (+)-SKF 10,047 > (+)-3-PPP > DTG > (-)-pentazocine > (-)-SKF 10,047. The potency of the putative Dg receptor-selective li gand (+/-)-7-OH-DPAT was close to that measured for (+)-pentazocine in displacement experiments. These data suggest that [H-3]-(+)-pentazoci ne labels sigma-1 sites in human cerebellum under appropriate assay co nditions.