[³H]-(+)-pentazocine binding to sigma recognition sites in human cerebellum

The binding characteristics of the sigma-1 selective benzomorphan [³H]-(+)-pentazocine were determined in human cerebellar membranes. Saturation 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 at 25°C demonstrated reversible binding with association with association and dissociation rate constants determined for two classes of sites. In saturation binding studies, the addition of (+)-SKF 10,047 occluded binding of [³H]-(+)-pentazocine to high affinity sigma binding sites. The affinity profile of ligands displacing [³H]-(+)-pentazocine was consistent 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 D₃ receptor-selective ligand (±)-7-OH-DPAT was close to that measured for (+)-pentazocine in displacement experiments. These data suggest that [³H]-(+)-pentazocine labels sigma-1 sites in human cerebellum under appropriate assay conditions.