title: 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-(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.
authors: Department of Psychopharmacology, Tokyo Institute of Psychiatry, Japan.
authors: H
authors: H
authors: Yamamoto
authors: T
authors: T
authors: Yamamoto
authors: N
authors: N
authors: Sagi
authors: S
authors: S
authors: Okuyama
authors: N
authors: N
authors: Kawai
authors: A
authors: A
authors: Baba
authors: T
authors: T
authors: Moroji
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D013287:Illicit Drugs / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007700:Kinetics; D008024:Ligands; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
chemical_list: D000840:Anisoles; D013287:Illicit Drugs; D008024:Ligands; D011437:Propylamines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D014316:Tritium; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D015544:Inositol 1,4,5-Trisphosphate; C012058:tenocyclidine; D002217:Carbachol; D010622:Phencyclidine