Polypharmacological Drugs in the Treatment of Epilepsy: The Comprehensive Review of Marketed and New Emerging Molecules

Epilepsy is a complex neurological disorder which has plagued the human population through the ages and continues to affect about 50 million people worldwide. A better understanding of the pathogenesis of epilepsy unmasks various molecular targets for the treatment of epilepsy. The currently used antiepileptic drugs (AEDs) predominately target voltage-gated ion channels (Na+γ, Ca2+γ and K+γ), GABAA receptor, glutamate receptor, synaptic vesicle 2A (SV2A) protein and carbonic anhydrase (CA). One group of AEDs acts on a single target while another group acts via multiple targets to control seizure episodes. AEDs which act via multiple mechanisms or polypharmacological mechanisms of action have appeared as broad spectrum anticonvulsant agent and therefore, they provide a better choice to clinicians to manage drug-resistant epilepsies and various other epileptic syndromes. For example, polypharmacological AEDs such as PB, VPA, OXC, FBM etc. are vital for managing epilepsy successfully, since decades. In literature there is no review available which exclusively highlights the polypharmacological mechanisms of action of existing AEDs as well as new emerging molecules. This review covers running marketed AEDs, clinical trial drugs as well as potent preclinical molecules which displayed anti-epileptic activity via multiple mechanisms of action and this appraisal will surely provide a base for discovering potent multi-targeted AEDs.