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Antiepileptic Drugs: How They Work in Headache
Author(s) -
Cutrer F. Michael
Publication year - 2001
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1046/j.1526-4610.2001.01154-2.x
Subject(s) - gabapentin , topiramate , pharmacology , migraine , glutamate receptor , valproic acid , anticonvulsant , epilepsy , medicine , neuroscience , chemistry , receptor , psychology , alternative medicine , pathology
Antiepileptic drugs (AEDs) are promising agents for the prevention of migraine and other head pain. Migraine and epilepsy share several clinical features and respond to many of the same pharmacologic agents, suggesting that similar mechanisms may be involved in their pathophysiology. The mechanisms of action of AEDs are not fully understood, and a single drug may have more than one mechanism, both in epilepsy and in migraine. Valproate, topiramate, and gabapentin are likely to affect nociception by modulating gamma‐aminobutyric acid‐ (GABA‐) and/or glutamate‐mediated neurotransmission. All three AEDs enhance GABA‐mediated inhibition. Valproate and gabapentin interfere with GABA metabolism to prevent its ultimate conversion to succinate, and topiramate potentiates GABA‐mediated inhibition by facilitating the action of GABA receptors. In addition, topiramate acts directly on non‐ N ‐methyl‐D‐aspartate, alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid/kainate glutamate receptors. Valproate, topiramate, and possibly gabapentin inhibit sodium ion channels. All three drugs modulate calcium ion channel activity. Valproate blocks T‐type calcium ion channels; topiramate inhibits high‐voltage‐activated L‐type calcium ion channels; and gabapentin binds to the α 2 δ subunit of L‐type calcium ion channels. AEDs may be useful in migraine prevention through such mechanisms as modulating the biochemical phenomena of aura or acting directly on the nociceptive system. Further evaluations of AEDs in migraine models will provide a better understanding of the pathophysiology and prevention of migraine.