title: Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders.
abstract: The mechanism of action of several antiepileptic drugs (AEDs) rests on their ability to modulate the activity of voltage-gated sodium currents that are responsible for fast action potential generation. Recent data indicate that lacosamide (a compound with analgesic and anticonvulsant effects in animal models) shares a similar mechanism. When compared with other AEDs, lacosamide has the unique ability to interact with sodium channel slow inactivation without affecting fast inactivation. This article reviews these findings and discusses their relevance within the context of neuronal activity seen during epileptiform discharges generated by limbic neuronal networks in the presence of chemical convulsants. These seizure-like events are characterized by sustained discharges of sodium-dependent action potentials supported by robust depolarizations, thus providing synchronization within neuronal networks. Generally, AEDs such as phenytoin, carbamazepine and lamotrigine block sodium channels when activated. In contrast, lacosamide facilitates slow inactivation of sodium channels both in terms of kinetics and voltage dependency. This effect may be relatively selective for repeatedly depolarized neurons, such as those participating in seizure activity in which the persistence of sodium currents is more pronounced and promotes neuronal excitation. The clinical effectiveness of lacosamide has been demonstrated in randomized, double-blind, parallel-group, placebo-controlled, adjunctive-therapy trials in patients with refractory partial seizures. Further studies should determine whether the effects of lacosamide in animal models and in clinical settings are fully explained 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.
authors: Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montréal, Québec, Canada.
authors: Giulia
authors: G
authors: Curia
authors: Giuseppe
authors: G
authors: Biagini
authors: Emilio
authors: E
authors: Perucca
authors: Massimo
authors: M
authors: Avoli
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D000078334:Lacosamide; D008958:Models, Molecular; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D015222:Sodium Channels; D000078334:Lacosamide