title: Binding characteristics of remoxipride and its metabolites to dopamine D2 and D3 receptors.
abstract: The substituted benzamide, remoxipride, is a new atypical antipsychotic agent with good clinical efficacy and low extrapyramidal side-effect potential. In the present study, the in vitro receptor binding properties of remoxipride and several of its metabolites to rat striatal dopamine D2 and cloned human dopamine D2A and D3 receptors were investigated. Remoxipride bound to [3H]raclopride-labelled dopamine D2 receptors in rat striatum with an affinity (Ki) of 113 nM. The significantly lower affinities of remoxipride reported when [3H]spiperone was used as a radioligand are suggested to be due to methodological problems associated with the use of very high-affinity radioligands. Some of the phenolic metabolites of remoxipride found mainly in rat exhibited considerably higher affinities to dopamine D2 and D3 receptors than remoxipride itself. The pyrrolidone metabolites found mainly in the human had very low dopamine D2 and D3 affinities. The present in vitro results suggest that the behavioural effects of remoxipride in rats may reflect the effect of remoxipride and some of its high-affinity metabolites.
authors.affiliation: Department of Neuropharmacology, CNS Preclinical R&D, Astra Arcus AB, Södertälje, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Mohell
authors.forename: M
authors.initials: M
authors.lastname: Sällemark
authors.forename: S
authors.initials: S
authors.lastname: Rosqvist
authors.forename: A
authors.initials: A
authors.lastname: Malmberg
authors.forename: T
authors.initials: T
authors.lastname: Högberg
authors.forename: D M
authors.initials: DM
authors.lastname: Jackson
mesh_terms: D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D003342:Corpus Striatum / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D051379:Mice; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D017330:Remoxipride / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
chemical_list: C493593:DRD3 protein, human; C493594:Drd3 protein, mouse; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D017330:Remoxipride; D020891:Raclopride; D013134:Spiperone