Differential Profile of Antipsychotics at Serotonin 5-ht1a and Dopamine D2s Receptors Coupled to Extracellular Signal-regulated Kinase.
From: Department of Cellular and Molecular Biology, Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, F 81106 Castres Cedex, France. liesbeth.bruins.slot@pierre-fabre.com
European journal of pharmacology
- Publish Date: Mar 2006
- ISSN: 0014-2999
- Volume: 534
- Issue: 1-3
- Pages: 63-70
- Medium: Print
- Language: English
- Citation (JAMA): Bruins Slot Liesbeth A, De Vries Luc, Newman-Tancredi Adrian, et al. Differential Profile of Antipsychotics at Serotonin 5-ht1a and Dopamine D2s Receptors Coupled to Extracellular Signal-regulated Kinase.. Eur. J. Pharmacol. Mar 2006;534:63-70
Abstract
The effects of antipsychotics targeting dopamine D2 and serotonin 5-HT1A receptors were compared with conventional antipsychotics on phosphorylation of Extracellular signal-Regulated Kinase 1/2 (ERK 1/2) in CHO cell lines stably expressing either the human serotonin 5-HT1A or human dopamine D2S receptor. All antipsychotics except haloperidol and olanzapine exhibited agonist properties at serotonin 5-HT1A receptors. Emax values (% effect of 10 microM 5-HT) were: bifeprunox (74), SSR181507 (73), SLV313 (72), aripiprazole (60), ziprasidone (56), clozapine (33). At dopamine D2S receptors, partial agonist activity (% effect of 10 microM dopamine) was observed for bifeprunox (76), SSR181507 (66) and aripiprazole (59). Other antipsychotics attenuated dopamine-induced ERK phosphorylation, with pK(B) values of : SLV313 (8.5), haloperidol (8.1), olanzapine (7.8), ziprasidone (7.7), and clozapine (6.4). Amongst the dopamine D2/serotonin 5-HT1A receptor compounds, aripiprazole acts as a partial dopamine D2S and serotonin 5-HT1A receptor agonist. SSR181507 and bifeprunox possess a profile of action similar to each other, efficaciously stimulating both serotonin 5-HT1A and dopamine D2S receptors. In contrast, SLV313, also an efficacious serotonin 5-HT1A receptor agonist, acted as a high potency dopamine D2 receptor antagonist. Thus, antipsychotics display varying efficacies at serotonin 5-HT1A and dopamine D2S receptors which may play a major role in their differential functional profiles in blocking the diverse symptoms of schizophrenia.
Mesh Headings (Keywords): Animals, Antipsychotic Agents, CHO Cells, Cricetinae, Cricetulus, Dioxanes, Dose-Response Relationship, Drug, Extracellular Signal-Regulated MAP Kinases, Phosphorylation, Piperazines, Quinolones, Receptor, Serotonin, 5-HT1A, Receptors, Dopamine D2, Signal Transduction, Transfection, Tropanes
Check for Full Text / PubMed Unique Identifier (PMID): 16497294
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