Faught Edward
Emory University, Neurology , 101 Woodruff Circle, Atlanta, GA 30322 , USA +1 404 778 3444 ; +1 404 778 4216 ;
Expert Opin Investig Drugs. 2014 Jan;23(1):107-13. doi: 10.1517/13543784.2014.848854. Epub 2013 Oct 23.
AMPA-type glutamate receptor (AMPAR) antagonism is under development as a novel mechanism of action for antiepileptic drugs. Selurampanel (BGG492) is an experimental competitive AMPA antagonist currently in clinical trials.
This article provides a review of the roles of glutamate receptors, especially of the AMPA type, in normal and epileptic synaptic transmission. It also provides a discussion of the mechanisms of action of AMPAR antagonist compounds. The article includes a summary of the preclinical and clinical data on the efficacy and safety of BGG492 and provides a discussion of the future role of these compounds in clinical therapy.
Since many persons with epilepsy remain inadequately treated, compounds exploiting new mechanisms for seizure control are welcome. Based on available clinical trial data as adjunctive therapy, the AMPAR antagonists will likely be highly useful in a small subset of persons and moderately helpful in a larger subset, similar to other new drugs for epilepsy developed since 1993. It remains impossible to predict which patients will respond to which class of drugs.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体（AMPAR）拮抗作用作为抗癫痫药物的一种新作用机制正在研发中。塞鲁拉潘（BGG492）是一种目前正在进行临床试验的实验性竞争性AMPA拮抗剂。
本文综述了谷氨酸受体，尤其是AMPA型受体在正常和癫痫性突触传递中的作用。还讨论了AMPAR拮抗剂化合物的作用机制。文章总结了关于BGG492疗效和安全性的临床前和临床数据，并讨论了这些化合物在临床治疗中的未来作用。
由于许多癫痫患者仍未得到充分治疗，利用新的癫痫控制机制的化合物受到欢迎。根据现有作为辅助治疗的临床试验数据，AMPAR拮抗剂可能对一小部分患者非常有用，对更大一部分患者有一定帮助，这与自1993年以来研发的其他新型抗癫痫药物类似。目前仍无法预测哪些患者会对哪类药物有反应。
