Discrimination of (+)-3-PPP sites from DTG sites by FH-510, a novel potent σ ligand, in rat brain

Abstract

The effect of 5,8-dimethyl-4-(2-di- n-propylaminoethyl)carbazol monohydrochloride (FH-510) on the binding of σ ligands such as [ 3 H](+)-3-(3- hydroxyphenyl)-N-(1- propyl)piperidine([ 3 H](+)-3- PPP) and [ 3 H]1,3- di-o- tolylguanidine ([ 3H]DTG) to rat brain membranes was studied. The inhibitory effect of FH-510 on [ 3H](+)-3-PPP binding to membranes of rat brain was 260 times more potent than that on [ 3H]DTG binding. Scatchard plot analysis showed that FH-510 inhibited [ 3H](+)-3-PPP binding in a competitive manner, while the inhibitory effect of FH-510 on [ 3H]DTG binding was noncompetitive. These results suggest that (+)-3-PPP sites could be discriminated from DTG sites, and that FH-510 binds preferentially to (+)-3-PPP recognition sites in rat brain.