The mechanism of action of several antiepileptic drugs (AEDs) rests on their ability tomodulate the activity of voltage-gated sodium currents that are responsible for fast action potentialgeneration. Recent data indicate that lacosamide - a compound with analgesic and anticonvulsanteffects in animal models - shares a similar mechanism. When compared with other AEDs, lacosamidehas the unique ability to interact with sodium channel slow inactivation without affecting fastinactivation. This article reviews these findings and discusses their relevance within the context ofneuronal activity seen during epileptiform discharges generated by limbic neuronal networks in thepresence of chemical convulsants. These seizure-like events are characterized by sustained dischargesof sodium-dependent action potentials supported by robust depolarizations thus providingsynchronization within neuronal networks. Generally, AEDs such as phenytoin, carbamazepine andlamotrigine block sodium channels when activated. By contrasts, lacosamide facilitates slowinactivation of sodium channels both in term of kinetics and voltage-dependency. This effect may berelatively selective for repeatedly depolarized neurons such as those participating in seizure activity inwhich the persistence of sodium currents is more pronounced and promotes neuronal excitation. Theclinical effectiveness of lacosamide has been demonstrated in randomized placebo-controlled doubleblindparallel-group, adjunctive-therapy trials in patients with refractory partial seizures. Furtherstudies should determine whether lacosamide effects in animal models and in clinical settings are fullyexplained by its selective action on sodium current slow inactivation or whether other effects (e.g.,interactions with the collapsin-response mediator protein 2) play a contributory role.

Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders / Curia, Giulia; Biagini, Giuseppe; E., Perucca; M., Avoli. - In: CNS DRUGS. - ISSN 1172-7047. - STAMPA. - 23:(2009), pp. 555-568. [10.2165/00023210-200923070-00002]

Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders

CURIA, GIULIA;BIAGINI, Giuseppe;
2009

Abstract

The mechanism of action of several antiepileptic drugs (AEDs) rests on their ability tomodulate the activity of voltage-gated sodium currents that are responsible for fast action potentialgeneration. Recent data indicate that lacosamide - a compound with analgesic and anticonvulsanteffects in animal models - shares a similar mechanism. When compared with other AEDs, lacosamidehas the unique ability to interact with sodium channel slow inactivation without affecting fastinactivation. This article reviews these findings and discusses their relevance within the context ofneuronal activity seen during epileptiform discharges generated by limbic neuronal networks in thepresence of chemical convulsants. These seizure-like events are characterized by sustained dischargesof sodium-dependent action potentials supported by robust depolarizations thus providingsynchronization within neuronal networks. Generally, AEDs such as phenytoin, carbamazepine andlamotrigine block sodium channels when activated. By contrasts, lacosamide facilitates slowinactivation of sodium channels both in term of kinetics and voltage-dependency. This effect may berelatively selective for repeatedly depolarized neurons such as those participating in seizure activity inwhich the persistence of sodium currents is more pronounced and promotes neuronal excitation. Theclinical effectiveness of lacosamide has been demonstrated in randomized placebo-controlled doubleblindparallel-group, adjunctive-therapy trials in patients with refractory partial seizures. Furtherstudies should determine whether lacosamide effects in animal models and in clinical settings are fullyexplained by its selective action on sodium current slow inactivation or whether other effects (e.g.,interactions with the collapsin-response mediator protein 2) play a contributory role.
23
555
568
Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders / Curia, Giulia; Biagini, Giuseppe; E., Perucca; M., Avoli. - In: CNS DRUGS. - ISSN 1172-7047. - STAMPA. - 23:(2009), pp. 555-568. [10.2165/00023210-200923070-00002]
Curia, Giulia; Biagini, Giuseppe; E., Perucca; M., Avoli
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