Intracellular CICR -associated pharmacological mechanism of action of antiepileptic drugs

Carbamazepine (CBZ) and zonisamide (ZNS) are antiepileptic drugs (AEDs) with multiple mechanisms of action, including inhibition of voltage-dependent sodium and calcium channels, enhancement of inhibitory events mediated by GABAergic neurotransmission, and blockade of the glutamatergic neurotransmission in the brain. Recently, the intracellular signaling pathways have been implicated as the new targets of AEDs. Especially, we have investigated the functional importance of Ca2+ mobilization, composed of influx through Ca2+ channels and output through ryanodine receptor (RyR)- and inositol-triphosphate receptor (IP3R)-sensitive intracellular Ca2+-induced Ca2+ releasing systems (CICRs), in the pathogenesis of epilepsy and the pharmacological mechanism of AEDs. In this review, we discuss the actions of CBZ and ZNS on neurotransmitter exocytosis associated with RyR-sensitive CICR. Further studies on the mechanisms of action of AEDs may help to understand the clinical benefits of AEDs in the treatment of epilepsy disorders.