Pharmacogenomics
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Genetic variability has recently been implicated in the development of familial epilepsy syndromes and in heterogeneous responses of epilepsy patients to drug treatment. Mutations in distinct proteins have been shown to underlie the development of epilepsy, increase propensity for drug resistance, and alter drug metabolism. Improved understanding of how individual genetic variability may alter the efficacy of pharmacological therapeutic interventions is an important and timely goal. The investigation of relationships between genotype and patient responses to drug treatment is termed pharmacogenomics.
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Interindividual differences in the experience of pain have been appreciated clinically for over a century. More recently, there has been a growing body of evidence demonstrating differences in analgesic response to various pharmacotherapies, although the source of this variability largely remains to be explained. To this end, basic science research is beginning to identify the allelic variants that underlie such antinociceptive variability using a multiplicity of animal models, and powerful genetic approaches are being exploited to accelerate this process. ⋯ Looking toward the future development of one or more widely utilised, pharmacogenetic screens that would lead to modifications in treatment planning, at least with respect to the pharmacologic management of pain, this review will document the breadth of genetically-based variability in drug-mediated antinociception in animals. Specific examples in which the gene or genes underlying such variability have been postulated or identified will be given, while highlighting the effect of sex and its interactions with other genetic backgrounds. Finally, we will summarise and evaluate the literature on pharmacogenetic differences in human analgesic drug response, for which the influence of sex has served as one of the better studied and heuristically insightful examples.