CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine.

Objectives: We observed that CYP2D6 contributes to pharmacodynamic tissue sensitivity to perphenazine as measured by the areas under the curve (AUCs) expressed as a ratio (prolactin-AUC0-6/perphenazine-AUC0-6) in Chinese Canadians [Pharmacogenetics and Genomics 2007; 17:339-347]. As genetic heterogeneity in drug targets can influence drug response, we sought to further evaluate the contribution of CYP2D6 to pharmacodynamic sensitivity in our previous study sample in tandem with DRD2, the primary molecular target for perphenazine.

Methods: Genotyping for DRD2 Taq1A, -141C ins/del and Ser311Cys functional polymorphisms was performed using PCR-restriction-fragment length polymorphism methods.

CYP2D6 genotype in relation to perphenazine concentration and pituitary pharmacodynamic tissue sensitivity in Asians: CYP2D6-serotonin-dopamine crosstalk revisited.

Objectives: Hyperprolactinemia is a common side effect of first-generation antipsychotics mediated by antagonism of dopaminergic neurotransmission in the pituitary. Most first-generation antipsychotics are metabolized by CYP2D6 in the liver. Further, CYP2D6 is expressed in the human brain as a 5-methoxyindolethylamine O-demethylase potentially contributing to regeneration of serotonin from 5-methoxytryptamine.

Pharmacogenetics and pharmacogenomics: origin, status, and the hope for personalized medicine.

Pharmacogenetics arose with studies of single genes, which had major effects on the action of particular drugs. It turned into pharmacogenomics through realization that the controls of most drug responses are multifactorial. Then, variable gene expression posed new problems, for example what do drugs do to genes, or how useful is any genetic pretesting of a person? A common disease may be caused by different groups of genes in different people, who therefore require different drugs for treatment.