DISCRIMINATION OF (+)-3-PPP SITES FROM DTG SITES BY FH-510, A NOVEL POTENT SIGMA-LIGAND, IN RAT-BRAIN

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