Key factors in the discovery and development of new antiepileptic drugs

被引:422
作者
Bialer, Meir [1 ,2 ]
White, H. Steve [3 ,4 ]
机构
[1] Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Res, Fac Med, IL-91120 Jerusalem, Israel
[2] Hebrew Univ Jerusalem, David R Bloom Ctr Pharm, Jerusalem, Israel
[3] Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA
[4] Univ Utah, Anticonvulsant Drug Dev Program, Salt Lake City, UT USA
关键词
SEVERE MYOCLONIC EPILEPSY; TEMPORAL-LOBE EPILEPSY; KAINATE-INDUCED EPILEPSY; AMYGDALA-KINDLED RATS; AMINOMETHYL)-1-CYCLOHEXANE ACETIC-ACID; SPONTANEOUS RECURRENT SEIZURES; SPONTANEOUS MOTOR SEIZURES; SYNAPTIC VESICLE PROTEIN; REDUCED SODIUM CURRENT; ADVERSE EVENT PROFILE;
D O I
10.1038/nrd2997
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Since the early 1990s, many new antiepileptic drugs (AEDs) that offer appreciable advantages in terms of their favourable pharmacokinetics, improved tolerability and lower potential for drug-drug interactions have entered the market. However, despite the therapeutic arsenal of old and new AEDs, approximately 30% of patients with epilepsy still suffer from seizures. Thus, there remains a substantial need for the development of more efficacious AEDs for patients with refractory seizures. Here, we briefly review the emerging knowledge on the pathological basis of epilepsy and how it might best be used in the design of new therapeutics. We also discuss the current approach to AED discovery and highlight some of the unique features of newer models of pharmacoresistance and epileptogenesis that have emerged in recent years.
引用
收藏
页码:68 / 82
页数:15
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