NE-100, a novel sigma ligand: effects on [3H]TCP binding to intact primary cultured neuronal cells

N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100), a potent and highly selective sigma ligand, haloperidol, (+)pentazocine, 1-(cyclopropyl-methyl)-4-(2'-(4"-fluorophenyl)-2'-oxoethyl) piperidine HBr (DuP 734) and 4-(2'-(4"-cyanophenyl)-2'-oxoethyl) 1-(cyclopropylmethyl)piperidine (XJ 448) inhibited carbachol-induced inositol 1,4,5-triphosphate (IP3) formation in a dose-dependent manner. The rank order of potency of the tested drugs for inhibition was: haloperidol > or = (+)pentazocine = NE-100 > DuP 734 = XJ 448. In addition, the effects of NE-100, DuP 734 and XJ 448 upon [3H]TCP binding were examined using primary cultured neuronal cells derived from the fetal rat telencephalon. These drugs inhibited [3H]TCP binding to intact cells. The ability of the test drugs to inhibit [3H]TCP binding to primary cultured neuronal cells was in the order: NE-100 > DuP 734 > XJ 448. These observations suggest that NE-100 indirectly modulates the N-methyl-D-aspartate (NMDA)/phencyclidine (PCP) receptor ion channel complex (NMDA receptor-ion channel), presumably through sigma-1 sites.