Sankar Raman, Lerner Jason T
David Geffen School of Medicine at UCLA, Mattel Children's Hospital at UCLA, Los Angeles, California 90095-1752, USA.
Int Rev Neurobiol. 2008;83:215-25. doi: 10.1016/S0074-7742(08)00012-3.
The teratogenic potential of an antiepileptic drug is determined by the chemical attributes of the molecule under discussion and the genetic attributes of the host. The role of the hepatic mixed function oxidase system may be especially important in conferring teratogenic risk. However, systems such as epoxide hydrolase, glutathione reductase, and superoxide dismutase and other toxin scavenging systems may be important modifiers that lower the risk. Genetic variability in these systems is important in determining the type and severity of the final outcome. While our knowledge of these factors is incomplete, progress can be achieved by beginning to include these concepts in our discussion on the topic and by promoting research that may improve our ability to individualize the analysis of risk for a specific patient with regard to specific antiepileptic drugs. Such an approach will most likely involve DNA microchip technology and has the potential to overcome some of the limitations of pregnancy registries. Such an approach may also lead to novel interventions and therapeutics design to lower the teratogenic potential of pharmacologic treatment of epilepsy during conception.
抗癫痫药物的致畸潜力取决于所讨论分子的化学特性以及宿主的遗传特性。肝混合功能氧化酶系统在赋予致畸风险方面的作用可能尤为重要。然而，诸如环氧化物水解酶、谷胱甘肽还原酶和超氧化物歧化酶等系统以及其他毒素清除系统可能是降低风险的重要调节因子。这些系统中的基因变异性对于确定最终结果的类型和严重程度很重要。虽然我们对这些因素的了解并不完整，但通过开始在我们关于该主题的讨论中纳入这些概念，并推动可能提高我们针对特定抗癫痫药物对特定患者进行个体化风险分析能力的研究，就可以取得进展。这种方法很可能涉及DNA微芯片技术，并且有可能克服妊娠登记的一些局限性。这种方法还可能导致新的干预措施和治疗设计，以降低受孕期间癫痫药物治疗的致畸潜力。
