Chirality as an Important Factor for the Development of New Antiepileptic Drugs.

Abstract

In recent years, chiral molecules (especially enantiomers) have occupied a significant place in pharmaceutical industry and have played a prominent role in the development of new drugs. Individual stereoisomers exhibit marked differences in pharmacodynamic, pharmacokinetic, and toxicological properties. Therefore, there is currently considerable interest in fully characterizing and examining both enantiomers in the early stages of new drug development. Despite the fact that epilepsy is a complex disease and that a given drug's mechanism of action may be multidirectional and not always fully understood, significant differences have been observed in the anticonvulsant activity of individual stereoisomers. Therefore, between 1996 and 2018, among 14 new antiepileptic drugs (AEDs) approved for the treatment of epilepsy, as many as seven are chiral and introduced to the market in the single-enantiomer (or diastereomer) form. This review provides an overview of the impact of chirality on the development and discovery of new AEDs that have entered into clinical trials or preclinical studies. These new AEDs were developed by applying the single-enantiomer approval strategy. Herein we focus our attention on the main synthetic pathways of stereoisomers, as well as on the influence of chirality on pharmacodynamic, pharmacokinetic, and/or toxicological properties.