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

Abstract N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100), a potent and highly selective sigma ligand, haloperidol, (+)pentazocine, 1-(cyclopropylmethyl)-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 (IP 3 ) formation in a dose-dependent manner. The rank order of potency of the tested drugs for inhibition was: haloperidol ≥ (+) pentazocine = NE −100 > DuP 734 = XJ 448 . In addition, the effects of NE-100, DuP 734 and XJ 448 upon [ 3 H]TCP binding were examined using primary cultured neuronal cells derived from the fetal rat telencephalon. These drugs inhibited [ 3 H]TCP binding to intact cells. The ability of the test drugs to inhibit [ 3 H]TCP binding to primary cultured neuronal cells was in the order: NE -100 > DuP 734 > XJ 448 . Thes 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.