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Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.
Author: BrannM R, BursteinE S, DavisR E, GaoY, HacksellU, KnappA E, MaJ, NashN R, OlssonR, PhamE, WeinerD M, WongS
Original Abstract of the Article :
Drugs that antagonize D2-like receptors are effective antipsychotics, but the debilitating movement disorder side effects associated with these drugs cannot be dissociated from dopamine receptor blockade. The "atypical" antipsychotics have a lower propensity to cause extrapyramidal symptoms (EPS), b...See full text at original site
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引用元：
https://doi.org/10.1124/jpet.105.092155
データ提供：米国国立医学図書館（NLM）
Unlocking the Mysteries of Antipsychotics: A Quest for Improved Treatment
Antipsychotics, like oases in the vast desert of mental illness, offer hope for patients battling schizophrenia and other psychotic disorders. This study delves into the molecular mechanisms of antipsychotics, examining their effects on dopamine receptors, specifically D2, D3, and D4. The researchers identified clozapine's metabolite, N-desmethylclozapine (NDMC), as a partial agonist at D2 and D3 receptors, potentially explaining the lower incidence of extrapyramidal symptoms (EPS) associated with clozapine.
NDMC: A Potential Key to Improved Antipsychotic Treatment
The study's findings suggest that NDMC, with its partial agonist properties at D2 and D3 receptors, may contribute to the effectiveness of clozapine as an antipsychotic with a lower risk of EPS. This discovery opens the possibility of bypassing clozapine blockade through direct administration of NDMC, potentially leading to enhanced antipsychotic efficacy and improved patient outcomes.
Navigating Antipsychotic Therapy with Precision
This research underscores the importance of understanding the molecular mechanisms of antipsychotics to optimize treatment strategies and minimize adverse effects. The identification of NDMC as a partial agonist at D2 and D3 receptors offers a promising avenue for further exploration, potentially leading to the development of new antipsychotic agents with improved efficacy and safety profiles.
Dr.Camel's Conclusion
The world of antipsychotics, like a vast desert, holds many mysteries. This study illuminates the importance of understanding the molecular mechanisms of these drugs to better navigate the challenges of mental illness. The discovery of NDMC as a partial agonist at D2 and D3 receptors opens a new pathway toward improved antipsychotic treatment, offering hope for patients seeking relief from the debilitating symptoms of psychotic disorders.
Date :
- Date Completed 2006-01-23
- Date Revised 2013-11-21
Further Info :
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