Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, oxcarbazepine and lacosamide

Practical guidance and considerations for transitioning patients from oxcarbazepine or carbamazepine to eslicarbazepine acetate — Expert opinion

“…Eslicarbazepine reduces voltage-gated sodium channel (VGSC) availability through enhancement of slow inactivation, whereas CBZ acts by altering fast inactivation of VGSC [19]. There are also other differences between eslicarbazepine and CBZ with regard to submaximal gamma-aminobutyric acid currents, K v 7.2 outward currents, and high-and low-affinity Ca v 3.2 inward currents [20].…”

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“…Based on these chemical properties, ESL has been developed for clinical use mainly to improve tolerability by reducing side effects of CBZ and OXC. Only recently, it has been reported that the effects these drugs exert on sodium channels seem to differ (Hebeisen et al, 2014). Doeser et al (2014a) now present two major novel findings concerning S-Lic/ESL.…”

“…The exact mechanism by which S-Lic leads to a slowing of recovery from fast inactivation in CBZ-resistant cases remains to be elucidated, since this cannot easily be explained by the additional mechanisms that have been described for S-Lic, i.e. enhancement of sodium channel slow inactivation (Hebeisen et al, 2014) and blockade of Ca V 3.2 channels (Doeser et al, 2014a). The different effects of CBZ and S-Lic on persistent sodium currents in the absence of the b 1 -subunit (Uebachs et al, 2010;Doeser et al, 2014b) cannot explain this either, as the lack of the b 1 -subunit did not influence recovery from fast inactivation (Uebachs et al, 2010), and the persistent current was modified equally by CBZ and S-Lic in the pilocarpine model (Doeser et al, 2014a).…”

Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate

“…Eslicarbazepine and its glucuronide metabolites account for 94 % of oral systemic exposure7; the minor active metabolites, R‐licarbazepine and oxcarbazepine, account for 5 % and 1 % of systemic exposure, respectively 8. Eslicarbazepine inhibits sodium currents by binding to voltage‐gated sodium channels and preferentially stabilizing the inactivated state of the channel 9. The apparent half‐life of eslicarbazepine is 13‐20 hours in plasma and ~20‐24 hours in cerebrospinal fluid 7, 8…”