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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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Lopez Rodriguez, RosarioAuthor

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May 5, 2022
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Pharmacodynamic genetic variants related to antipsychotic adverse reactions in healthy volunteers

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

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

Affiliations

Fdn Jimenez Diaz, Inst Invest Sanitaria, Dept Genet & Gen, E-28040 Madrid, Spain - Author
Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Liver Unit, Gastroenterol Serv, Madrid 28006, Spain - Author
Hosp Univ Princesa, Inst Teofilo Hernando, Inst Invest Sanitaria Princesa IIS IP, Serv Clin Pharmacol, Madrid, Spain - Author
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepatitos & Di, Madrid, Spain - Author
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain - Author
Univ Autonoma Madrid, Hosp Univ La Paz, Sch Med, Dept Pharmacol,Serv Clin Pharmacol, Madrid, Spain - Author
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Abstract

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.

Keywords

Adverse reactionAssociationAtypical antipsychoticsCyp2d6 genotypeDopamine-d-2 receptor geneExtrapyramidal symptomsGenetic markerOlanzapinePromoter polymorphismQuetiapineRisperidoneSchizophreniaSerotoninTardive-dyskinesiaWeight-gain

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Pharmacogenomics due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2013, it was in position 59/256, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-10-07:

  • WoS: 8
  • Scopus: 8

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-10-07:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 46 (PlumX).