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

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Zhang X, Hodgetts K, Rachwal S, Zhao H, Wasley JW, Craven K, Brodbeck R, Kieltyka A, Hoffman D, Bacolod MD, Girard B, Tran J, Thurkauf A

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

J Med Chem. 2000 Oct 19;43(21):3923-32.

PubMed ID
11052797 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ClozapineDopamine D2 receptorIC 50 (nM)113N/AN/ADetails
ClozapineDopamine D4 receptorIC 50 (nM)17N/AN/ADetails
HaloperidolDopamine D2 receptorKi (nM)7N/AN/ADetails
HaloperidolDopamine D2 receptorIC 50 (nM)4N/AN/ADetails
RemoxiprideDopamine D2 receptorIC 50 (nM)880N/AN/ADetails
RemoxiprideDopamine D4 receptorIC 50 (nM)3872N/AN/ADetails