A Candidate Pathway Strategy for Integration of Pharmacogenomic Components of Variability in Antipsychotic Treatment Outcomes: A Focus on Aripiprazole
Aripiprazole can induce a diverse range of effects at dopamine D2 receptors (agonism, antagonism, partial agonism) depending on the cellular milieu defined by promiscuous interactions with a host of signaling partners and variability in local G protein complement and concentration. This diversity provides an opportunity to illustrate the importance of integrating data on genetic variation in pharmacokinetic pathways and molecular targets for antipsychotics including biogenic amine receptors and their downstream signaling partners. Theragnostics, a new subspecialty of molecular medicine formed by combination of therapeutics with diagnostics, offers the potential to synthesize different types of biomarkers (DNA and protein-based) in the context of antipsychotic treatment outcomes. Because the dopamine receptor genetic variation is extensively reviewed elsewhere, we discuss the pharmacogenomic significance of variability in genes encoding for the 5-HT1A (HTR1A) and 5-HT2A (HTR2A) receptors and CYP2D6- and CYP3A4-mediated aripiprazole metabolism. As the field moves toward predictive genetic testing for newer antipsychotics, we emphasize the need for collaboration among pharmacogeneticists, bioethicists and specialists in science and technology studies.
Document Type: Review Article
Affiliations: Biomarker and Clinical Pharmacology Unit, VA Long Beach Healthcare System and Department of Psychiatry and Human Behavior, University of California Irvine, 5901 East Seventh Street, Long Beach, CA 90822, USA.
Publication date: 2005-12-01
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