Genetic predisposition to neuroleptic malignant syndrome : implications for antipsychotic therapy.
Genetic predisposition to neuroleptic malignant syndrome : implications for antipsychotic therapy.
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抗精神病药物恶性综合征的遗传倾向：抗精神病药物治疗的影响。
DOI：
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
C. Kawanishi
中科院分区：
文献类型：
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作者：
C. Kawanishi
抗精神病药恶性综合征（NMS）是抗精神病药的一种潜在致死性副作用，其发病机制尚不清楚。除了获得性风险因素外，临床观察表明许多遗传因素使患者易患NMS。药物遗传学的最新研究结果表明，药物代谢酶、药物转运蛋白和可能的药物靶向分子的遗传多态性与药物疗效和不良反应的个体间差异有关。遗传关联研究试图确定影响NMS易感性的多态性，特别是多巴胺D（2）受体、5-羟色胺受体和细胞色素p450 2D 6。虽然少数候选多态性与NMS相关，但需要进行大型对照研究以获得统计功效。另一方面，NMS可能包括具有共同特征症状但不同致病机制的异质性条件。对具有已确定的基因突变或多态性的个体的进一步分析应该促进我们对NMS潜在机制的理解。
The pathogenetic mechanism of neuroleptic malignant syndrome (NMS), a potentially lethal adverse effect of antipsychotics, is not well understood. In addition to acquired risk factors, clinical observations suggest a number of genetic factors predisposing patients to NMS. Recent findings in pharmacogenetics indicate that the genetic polymorphisms for drug-metabolizing enzymes, drug transporters, and possibly drug-targeting molecules, are associated with the interindividual differences in drug responses concerning both efficacy and adverse reactions. Genetic association studies have sought to identify polymorphisms influencing susceptibility to NMS, especially with respect to the dopamine D(2) receptor, serotonin receptor, and cytochrome p450 2D6. While a few candidate polymorphisms were associated with NMS, a large controlled study is needed to attain statistical power. On the other hand, NMS might include heterogeneous conditions with common characteristic symptoms but different causative mechanisms. Further analysis of individuals with identified genetic mutations or polymorphisms should advance our understanding of mechanisms underlying NMS.