The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditionsNature Med (2004)
AbstractAntiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including migraine headache, chronicneuropathic pain, mood disorders, schizophrenia and various neuromuscular syndromes. In many of these conditions, as in epilepsy, the drugs act by modifying the excitability of nerve (or muscle) through effects on voltage-gated sodium and calciumchannels or by promoting inhibition mediated by γ-aminobutyric acid (GABA) A receptors. In neuropathic pain, chronic nerveinjury is associated with the redistribution and altered subunit compositions of sodium and calcium channels that predisposeneurons in sensory pathways to fire spontaneously or at inappropriately high frequencies, often from ectopic sites. AEDs maycounteract this abnormal activity by selectively affecting pain-specific firing; for example, many AEDs suppress high-frequencyaction potentials by blocking voltage-activated sodium channels in a use-dependent fashion. Alternatively, AEDs may specificallytarget pathological channels; for example, gabapentin is a ligand of α2δvoltage-activated calcium channel subunits that areoverexpressed in sensory neurons after nerve injury. Emerging evidence suggests that effects on signaling pathways that regulateneuronal plasticity and survival may be a factor in the delayed clinical efficacy of AEDs in some neuropsychiatric conditions,including bipolar affective disorder.
Publication DateJuly, 2004
Citation InformationMichael A. Rogawski and Wolfgang Löscher. "The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions" Nature Med Vol. 10 Iss. 7 (2004)
Available at: http://works.bepress.com/michael_rogawski/10/