The possible use of the L-type calcium channel antagonist verapamil in drug-resistant epilepsy

Multidrug transporters (MDTs) are likely to play a role in the pathogenesis of drug resistance in epilepsy, acting at the level of the blood-brain barrier by returning antiepileptic drugs to the blood vessels and lowering brain penetration and concentration (e.g. the so-called multidrug transporter hypothesis). In the last ten years experimental studies on both animal models and human brain tissues have highlighted a potential role of the P-glycoprotein-one of the multidrug transporters of the blood-brain barrier-in the pathophysiology of drug-resistant epilepsies. At the same time, verapamil has been administered to patients with drug-resistant epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, focal epilepsies) or status epilepticus with promising results. In this drug profile paper the authors review current knowledge and main published studies regarding the role of the L-type calcium channel antagonist verapamil in drug-resistant epilepsy.