title: Pharmacodynamic genetic variants related to antipsychotic adverse reactions in healthy volunteers.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver 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
authors.forename: Rosario
authors.initials: R
authors.lastname: López-Rodríguez
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabaleiro
authors.forename: Dolores
authors.initials: D
authors.lastname: Ochoa
authors.forename: Manuel
authors.initials: M
authors.lastname: Román
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Borobia
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Carcas
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Jesús
authors.initials: J
authors.lastname: Novalbos
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D054316:Biomarkers, Pharmacological; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D000071058:Huntingtin Protein; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; C581293:DRD2 protein, human; D003987:Dibenzothiazepines; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine