N-methyl-D-aspartate receptor antagonists for migraine: a potential therapeutic approach

Migraine is one of the most common neurological disorders and still remains incurable. New targets for potential pharmacological intervention should be explored and evaluated for effective long-term management of patients with migraine. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels widely expressed in the central nervous system. NMDAR activation has been suggested to be implicated in trigeminovascular system and cortical spreading depression, which are involved in the mechanisms of migraine. Thus, it is reasonable to infer that NMDAR antagonists may provide a potentially novel therapeutic approach to the treatment of migraine. So far, no controlled clinical trial has been published that examines the efficacy of NMDAR antagonist for migraine prophylaxis. It is to be hoped that further studies of NMDAR antagonists, especially NR2B-selective and low-affinity antagonists, will enable the potential of these drugs to be fully tested.