title: FH-510, a potent and selective ligand for rat brain sigma recognition sites.
abstract: FH-510 (5,8-dimethyl-4-(2-di-n-propylaminoethyl)carbazol) is a potent ligand for sigma ligand binding sites in rat brain membranes and has an IC50 value of 4.8 +/- 1.0 nM, which is comparable to that of haloperidol (2.2 +/- 0.2 nM). The high selectivity of FH-510 for sigma binding sites was evaluated by its lack of significant affinity for other binding sites, including those for dopamine D2 and phencyclidine. When administered to mice orally, FH-510 suppressed (+)-N-allylnormetazocine ((+)-SKF10,047)-induced stereotyped behavior with an ED25 value of 0.54 mg/kg, which is 14-fold more potent than that for (+)-alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol ((+)-BMY14802) (7.6 mg/kg). These results suggest that FH-510 may be a potent and selective sigma ligand.
authors.affiliation: Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Chaki
authors.forename: Y
authors.initials: Y
authors.lastname: Imagawa
authors.forename: S
authors.initials: S
authors.lastname: Okuyama
authors.forename: M
authors.initials: M
authors.lastname: Muramatsu
authors.forename: S
authors.initials: S
authors.lastname: Otomo
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002227:Carbazoles / Q000378:metabolism* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000378:metabolism; D008297:Male; D051379:Mice; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000378:metabolism; D011437:Propylamines / Q000378:metabolism* / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D002227:Carbazoles; D011437:Propylamines; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C083362:FH 510; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; D006220:Haloperidol; D004298:Dopamine