title: Dopamine receptor binding of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)- 4-oxobutyl]-1,2,3,6-tetrahydropyridine (HPTP), an intermediate metabolite of haloperidol.
abstract: The neuroleptic agent haloperidol (HP) is biotransformed to metabolites such as 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine (HPTP) and 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium (HPP+). In this study, radioligand binding studies were performed using [3H]SCH23390 as a dopamine D1 receptor ligand and [3H]spiperone as a D2 ligand. Ki values for D1 receptors were 35.8 microM and 54.9 microM for HP and HPTP, respectively. Corresponding values for D2 receptors were 39.1 nM and 329.8 nM. These results indicate similar low affinities in the micromolar range for both HP and HPTP at the dopamine D1 receptor, a much higher affinity of both HP and HPTP for the D2 receptor than for the D1 receptor, and that HPTP binds to D2 receptors with a 9-fold lower affinity than HP. The data are consistent with observations in mice that HPTP is a much less potent acute neuroleptic agent than HP.
authors: Department of Pharmacology, Potchefstroom University for C.H.E., South Africa.
authors: L
authors: L
authors: Brand
authors: D W
authors: DW
authors: Oliver
authors: C J
authors: CJ
authors: van der Schyf
authors: S M
authors: SM
authors: Pond
authors: N
authors: N
authors: Castagnoli
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism*; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D014316:Tritium
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D013134:Spiperone; C101091:4(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)-1,2,3,6-tetrahydropyridine; D006220:Haloperidol