The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions.
Antiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including migraine headache, chronic neuropathic 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 calcium channels or by promoting inhibition mediated by gamma-aminobutyric acid (GABA) A receptors. In neuropathic pain, chronic nerve injury is associated with the redistribution and altered subunit compositions of sodium and calcium channels that 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. Alternatively, 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. Emerging evidence suggests that effects on signaling pathways that regulate neuronal plasticity and survival may be a factor in the delayed clinical efficacy of AEDs in some neuropsychiatric conditions, including bipolar affective disorder.
Rogawski
Michael A
MA
Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. michael.rogawski@nih.gov
Löscher
Wolfgang
W
D000927:Anticonvulsants / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy; D015220:Calcium Channels / Q000502:physiology; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy; D009468:Neuromuscular Diseases / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy; D015222:Sodium Channels / Q000502:physiology
D000927:Anticonvulsants; D015220:Calcium Channels; D015222:Sodium Channels