NE-100, A NOVEL SIGMA-LIGAND - EFFECTS ON [H-3] TCP BINDING TO INTACTPRIMARY CULTURED NEURONAL CELLS

-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride ( NE-100), a potent and highly selective sigma ligand, haloperidol, (+)p entazocine, l)-4-(2'-(4''-fluorophenyl)-2'-oxoethyl)piperidine HBr (Du P 734) and henyl)-2'-oxoethyl)1-(cyclopropylmethyl)piperidine (XJ 448) inhibited carbachol-induced inositol 1,4,5-triphosphate (IP3) formati on in a dose-dependent manner. The rank order of potency of the tested drugs for inhibition was: haloperidol greater than or equal to (+)pen tazocine = NE-100 > DuP 734 = XJ 448. In addition, the effects of NE-1 00, DuP 734 and XJ 448 upon [H-3]TCP binding were examined using prima ry cultured neuronal cells derived from the fetal rat telencephalon. T hese drugs inhibited [H-3]TCP binding to intact cells. The ability of the test drugs to inhibit [H-3]TCP binding to primary cultured neurona l cells was in the order: NE-100 > DuP 734 > XJ 448. These observation s suggest that NE-100 indirectly modulates the N-methyl-D-aspartate (N MDA)/phencyclidine (PCP) receptor ion channel complex (NMDA receptor-i on channel), presumably through sigma-1 sites.