Pharmacodynamic genetic variants related to antipsychotic adverse reactions in healthy volunteers
Rosario López-Rodríguez1, Teresa Cabaleiro, Dolores Ochoa
1Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Diego de Leon 62, 3ª, 28006 Madrid, Spain. rosario.lopez.rodriguez@uam.es
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. Original submitted 7 February 2013; Revision submitted 3 June 2013.
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Principles of Pharmacogenetics: Types of Genetic Variants
Drug toxicity: Idiosyncratic Reactions
Pharmacogenetics and Pharmacogenomics: Overview
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

