title: The dopamine D3 receptor partial agonist, BP 897, is an antagonist at human dopamine D3 receptors and at rat somatodendritic dopamine D3 receptors.
abstract: Recent studies have fueled the interest in dopamine D3 receptor antagonists and partial agonist for the treatment of psychosis and drug abuse, respectively. N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]naphthalene-2-carboxamide (BP 897) is a dopamine D3 receptor selective ligand recently described as partial agonist with potential effects on drug-dependence. The aim of the present study was to determine both the functional activity of BP 897 at human dopamine D3 receptors expressed in Chinese hamster ovary (CHO) cells and in an electrophysiological in vivo model of dopaminergic activity. BP 897 failed to stimulate the human dopamine D3 receptor and showed antagonistic effects (cpIC(50)=9.51) in a [(35)S]GTPgammaS binding assay in cells expressing the human dopamine D3 receptor. In vivo, BP 897 up to 8.2 mg/kg, i.v., had no agonistic effects on firing rate of substantia nigra dopaminergic neurons and antagonized the quinpirole-induced inhibition of firing (DID(50)=1.1 mg/kg). Our data demonstrate that BP 897 acts, in vivo and in vitro, as a dopamine D3 receptor antagonist.
authors.affiliation: Department of Pharmacology, Knoll AG, D- 67008 Ludwigshafen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wicke
authors.forename: J
authors.initials: J
authors.lastname: Garcia-Ladona
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010078:Oxazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D010078:Oxazines; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013462:Sulfur Radioisotopes; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D019257:Quinpirole; C120565:BP 897; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine