Activity of aromatic substituted phenylpiperazines lacking affinity for dopamine binding sites in a preclinical test of antipsychotic efficacy
| Autor: | Gregory E. Martin, Robert J. Elgin, Richard P. Shank, Joanne R. Mathiasen, Coralie B. Davis, William J. Baldy, Cynthia L. Fedde, James M. Kesslick, Deena L. DiStefano, Malcom K. Scott |
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| Rok vydání: | 1989 |
| Předmět: |
Dopamine binding
Dose-Response Relationship Drug Pharmacology Piperazines Rats Receptors Dopamine Structure-Activity Relationship Piperazine chemistry.chemical_compound Mechanism of action chemistry Dopamine Dopamine receptor Receptors Serotonin Drug Discovery Avoidance Learning medicine Animals Molecular Medicine medicine.symptom Binding site Receptor 5-HT receptor Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 32:1052-1056 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00125a020 |
| Popis: | Generally, antipsychotic agents are dopamine receptor blocking agents that also block conditioned avoidance responding (CAR) in the rat. Recently, however, both (Q-methoxyphenyl)piperazine (OMPP, 1h) and (m-chlorophenyl)piperazine (MCPP, 1o) have been reported to block conditioned avoidance responding in the rat although neither has dopamine receptor blocking properties. The present paper examines the behavioral and biochemical profile of a number of additional substituted phenylpiperazines. None of the phenylpiperazines tested demonstrated high affinity for either dopamine D-1 or D-2 receptor sites, yet many were effective in blocking CAR. The results suggest that the phenylpiperazines may be effective antipsychotic agents without blocking dopamine receptors. Moreover, the active compounds did demonstrate activity in displacing ligand binding to serotonin receptors. Receptor binding profiles were determined for 5-HT-1A and 5-HT-1B binding sites as well as for 5-HT-2 sites. The data from this preclinical test suggest these phenylpiperazines might be effective antipsychotic agents acting via a nondopaminergic mechanism of action. |
| Databáze: | OpenAIRE |
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