Pharmacogenetic assessment of antipsychotic-induced movement disorders: contribution of the dopamine D3 receptor and cytochrome P450 1A2 genes.
Tardive dyskinesia (TD) is characterized by involuntary movements predominantly in the orofacial region and develops in approximately 20% of patients during long-term treatment with typical antipsychotics. The high prevalence of TD and its disabling and potentially irreversible clinical course is an important shortcoming for treatment with typical antipsychotics. The studies presented in this article evaluate the role of single nucleotide polymorphisms in dopamine D3 receptor (DRD3) and CYP1A2 genes for propensity to develop TD in patients with schizophrenia. In theory, a combined pharmacogenetic analysis of pharmacokinetic and pharmacodynamic targets for antipsychotics should improve our ability to identify subpopulations that differ in drug safety profile. This information may in turn contribute to the design of more efficient clinical trials and thus expedite the development and regulatory approval of newer antipsychotic compounds.
Ozdemir
V
V
Neurogenetics Section, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Canada.
Basile
V S
VS
Masellis
M
M
Kennedy
J L
JL
D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019388:Cytochrome P-450 CYP1A2