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The study was supported by Fondo de Investigaciones Sanitarias (FIS-EC07/90466) of Instituto de Salud Carlos III, Madrid, Spain and by Fundacion Teofilo Hernando, a non-profit foundation linked to Universidad Autonoma de Madrid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Pharmacodynamic genetic variants related to antipsychotic adverse reactions in healthy volunteers

Publicat a:Pharmacogenomics. 14 (10): 1203-1214 - 2013-07-01 14(10), DOI: 10.2217/PGS.13.106

Autors: Lopez-Rodriguez, Rosario; Cabaleiro, Teresa; Ochoa, Dolores; Roman, Manuel; Borobia, Alberto M; Carcas, Antonio J; Ayuso, Carmen; Novalbos, Jesus; Abad-Santos, Francisco

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Aim: Clinical trials with healthy volunteers are a useful model for evaluating safety and tolerability, without the interference of concomitant diseases and drugs. The present study aims to improve our understanding of antipsychotic-related adverse reactions (ARs) and their possible association with common genetic variants of pharmacodynamic proteins such as neurotransmitter receptors/transporters. Materials & methods: A total of eight polymorphisms located in seven pharmacodynamic-related genes (SCL6A4, MDR1, 5HT2A, DRD2, DRD3, COMT and GRIN2B) were genotyped in a cohort of 211 healthy volunteers who received a single dose of risperidone (1 mg), olanzapine (5 mg) or quetiapine (25 mg). Results: Interestingly, a significant association was found between the incidence of neurological ARs and specific polymorphisms in key genes (DRD2 and SCL6A4). Conclusion: Genetic variants in pharmacodynamic genes could represent valuable markers of AR risk and antipsychotic safety.

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