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Epilepsies

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Quels sont les modes d’action des médicaments antiépileptiques qui sous- tendent leur usage dans d’autres domaines que celui des épilepsies ? Volume 17, issue 4, Octobre-Novembre-Décembre 2005

Author
Neurologie, Épileptologie, Université Pierre et Marie Curie (PARIS VI), Inserm U224, CHU Pitié-Salpêtrière, 47, bd de l’Hôpital, 75013 Paris

Antiepileptic agents are commonly used in non-epileptic conditions, including migraine, chronic neuropathic pain, mood disorders, and various neuromuscular syndromes. The action of AEDs at the level of ion channels or their receptors is presumed to modify neuronal excitability. Voltage-gated sodium channels, calcium channels are the main targets to reduce depolarization, whilst inhibition mediated by Gamma-aminobutyric acid (GABA) A receptors is promoted in order to increase hyperpolarisation. In peripheral neuropathic pain, chronic nerve injury is associated with the redistribution and altered subunit compositions of sodium and calcium channels. This plastic changes may predispose neurons in sensory pathways to fire spontaneously or at inappropriately high frequencies, often from ectopic sites. AEDs may counteract this abnormal activity by selectively affecting pain-specific firing ; for example, many AEDs suppress high-frequency action potentials by blocking voltage-activated sodium channels in a use-dependent fashion. In some situations, AEDs may specifically target pathological channels ; for example, gabapentin is a ligand of alpha2delta voltage-activated calcium channel subunits that are overexpressed in sensory neurons after nerve injury. Several lines of evidence suggest that the mood stabilizer functions of certain AEDs are derive from other mechanisms than direct action on in channels. They could modify the cell signalling system and lead to longer term cellular changes that are compatible, in terms of delay of action, with their mood stabilizing effect. These properties on cellular signalling system may be implicated in their teratogenic effects.