title: trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents.
abstract: The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D(2) and D(4) receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dichlorophenyl)piperazine (5m) and (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D(2) and D(4) receptors and had a D(2)/D(4) ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.
authors.affiliation: Neurogen Corporation, 35 Northeast Industrial Road, Branford, Connecticut 06405, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Hodgetts
authors.forename: S
authors.initials: S
authors.lastname: Rachwal
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: J W
authors.initials: JW
authors.lastname: Wasley
authors.forename: K
authors.initials: K
authors.lastname: Craven
authors.forename: R
authors.initials: R
authors.lastname: Brodbeck
authors.forename: A
authors.initials: A
authors.lastname: Kieltyka
authors.forename: D
authors.initials: D
authors.lastname: Hoffman
authors.forename: M D
authors.initials: MD
authors.lastname: Bacolod
authors.forename: B
authors.initials: B
authors.lastname: Girard
authors.forename: J
authors.initials: J
authors.lastname: Tran
authors.forename: A
authors.initials: A
authors.lastname: Thurkauf
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050638:Receptors, Dopamine D4; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C415570:1-((2-phenylcyclopropyl)-methyl)-4-(2,4-dimethylphenyl)piperazine; C415569:1-((2-phenylcyclopropyl)methyl)-4-(2,4-dichlorophenyl)piperazine; D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; C493601:Drd4 protein, rat; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D003577:Cytochrome P-450 Enzyme System