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

The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopro pyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for t he D-2 and D-4 receptors in a ratio similar to that observed for the atypic al neuroleptic clozapine. The compounds (1S,2S)-trans-1-[(2-phenylcycloprop yl)methyl]-4-(2,4-dichlorophenyl)piperazine (5m) and (1S,2S)-trans-1-[(2-ph enylcyclopropyl)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 rati o approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.