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OBJECTIVE To assess whether polymorphisms in the dopamine receptor genes and in the dopamine transporter gene (DAT ) are predictors of adverse effects of L -dopa. METHODS A retrospective noninterventional study with 183 patients with PD was conducted. Nine polymorphisms of the dopamine D2 receptor (DRD2 ), two of the dopamine D3 receptor (DRD3 ), three of(More)
The analgesic drug tramadol is bioactivated by CYP2D6 to the opioid receptor agonist O-desmethyltramadol. Case reports indicated that carriers of the CYP2D6 gene duplication may be at high risk for opioid adverse events. However, the effects of the CYP2D6 duplication on kinetics and dynamics of tramadol have not been systematically studied. Pharmacokinetics(More)
Genetic factors contribute to the phenotype of drug response. We systematically analyzed all available pharmacogenetic data from Medline databases (1970-2003) on the impact that genetic polymorphisms have on positive and adverse reactions to antidepressants and antipsychotics. Additionally, dose adjustments that would compensate for genetically caused(More)
Extrapyramidal adverse symptoms (EPS) represent a major type of adverse events in treatment with typical antipsychotic drugs which share high affinity to the dopamine D(2) receptor (DRD2). Genetic variants of this receptor may modulate the therapeutic response and the severity of adverse symptoms of antipsychotics. We analyzed nine known polymorphisms of(More)
OBJECTIVE This review aimed to provide distinct dose recommendations for antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and CYP2C19. This approach may be a useful complementation to clinical monitoring and therapeutic drug monitoring. METHOD Our literature search covered 32 antidepressants marketed in Europe, Canada, and the(More)
RATIONALE Perazine (PER) is a phenothiazine antipsychotic drug frequently used in Germany that undergoes extensive metabolism. OBJECTIVES AND METHODS To anticipate metabolic drug interactions and to explore the relevance of polymorphisms of metabolic enzymes, perazine-N-demethylation and perazine-N-oxidation were investigated in vitro using human liver(More)
Extracts of St. John's wort (Hypericum perforatum) are used in treatment of depression. They contain various substances with the naphthodianthrones hypericin and pseudohypericin as characteristic ingredients. These compounds were shown to cause phototoxicity in cell culture and in animals. A placebo-controlled randomized clinical trial with monitoring of(More)
The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may increase the susceptibility to(More)
Little is known about the impact of cytochrome P450 polymorphisms on the metabolism of trimipramine, which is still widely used as antidepressant due to its positive effect on sleep patterns. A single oral dose of 75 mg trimipramine was given to 42 healthy volunteers selected according to their CYP2D6, CYP2C19, and CYP2C9 genotypes. The reference group(More)
Antidepressant drug therapy is characterized by a high rate of therapeutic failure. There is increasing evidence that genetic factors are contributing to the inter-individual variability in antidepressant drug response. Genetic variability is described in both the pharmacokinetic part of drug action as well as in pharmacodynamic structures mediating drug(More)