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

Abstract

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.

Keywords:

• Seizures
• multidrug transporters
• P-glycoprotein
• blood-brain barrier
• verapamil
• epilepsy