Eslicarbazepine acetate (BIA 2-093)

摘要

Eslicarbazepine acetate (ESL) [( )-(−)-10-acetoxy-10, 11-dihydro-5 -dibenz[ ]azepine-5-carboxamide], formerly known as BIA 2-093, is a novel central nervous system (CNS)-active compound with anticonvulsant activity. It behaves as a voltage-gated sodium channel (VGSC) blocker and is currently under clinical development for the treatment of epilepsy and bipolar disorder. ESL shares with carbamazepine and oxcarbazepine the dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally different at the 10,11-position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine-10,11 epoxide. In pharmacokinetic studies in humans, ESL was rapidly and extensively metabolized to eslicarbazepine (S-licarbazepine), which is responsible for pharmacological activity. ESL has been tested in patients with refractory partial-onset seizures and was found to be efficacious and well tolerated. Monotherapy studies in adult epileptic patients and add-on studies in epileptic children are in the planning process. The efficacy and safety data appear to be very promising considering the refractory nature of the epileptic population enrolled in studies to date. Results of ongoing phase III studies in adult epileptic patients are expected to be available in 2007 and are required to define the position of ESL in the therapy of patients with epilepsy.