trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines: Mixed dopamine D2/D4 receptor antagonists as potential antipsychotic agents

Article abstract of DOI:10.1021/jm990562x

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 D₂ and D₄ 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)piperazin e (5m) and (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazin e (5t) were selected for functional antagonists at D₂ and D₄ receptors and had a D₂/D₄ ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.