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.
MeSH terms
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Animals
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Antipsychotic Agents / chemical synthesis*
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Antipsychotic Agents / chemistry
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Antipsychotic Agents / pharmacology
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CHO Cells
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Cricetinae
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Cytochrome P-450 Enzyme System / metabolism
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Dopamine Antagonists / chemical synthesis*
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Dopamine Antagonists / chemistry
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Dopamine Antagonists / pharmacology
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Humans
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In Vitro Techniques
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Male
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Microsomes, Liver / metabolism
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Adrenergic, alpha-1 / metabolism
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Receptors, Dopamine D2 / drug effects*
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Receptors, Dopamine D2 / metabolism
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Receptors, Dopamine D4
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Stereoisomerism
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Structure-Activity Relationship
Substances
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1-((2-phenylcyclopropyl)-methyl)-4-(2,4-dimethylphenyl)piperazine
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1-((2-phenylcyclopropyl)methyl)-4-(2,4-dichlorophenyl)piperazine
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Antipsychotic Agents
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DRD4 protein, human
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Dopamine Antagonists
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Drd4 protein, rat
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Piperazines
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Receptors, Adrenergic, alpha-1
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Receptors, Dopamine D2
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Receptors, Dopamine D4
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Cytochrome P-450 Enzyme System