trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: Mixed Dopamine D2/D4 Receptor Antagonists as Potential Antipsychotic Agents

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.