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, 15 (2), 361-370

Glutamate and Its Receptors as Therapeutic Targets for Migraine


Glutamate and Its Receptors as Therapeutic Targets for Migraine

Jan Hoffmann et al. Neurotherapeutics.


There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling. Animal studies indicate that glutamate plays a key role in pain transmission, central sensitization, and cortical spreading depression. Multiple therapies that target glutamate receptors including magnesium, topiramate, memantine, and ketamine have been reported to have efficacy in the treatment of migraine, although with the exception of topiramate, the evidence for the efficacy of these therapies is not strong. Also, because all of these therapies have other mechanisms of action, it is not possible to conclude that the efficacy of these drugs is entirely due to their effects on glutamate receptors. Further studies are needed to more clearly delineate the possible roles of glutamate and its specific receptor subtypes in migraine and to identify new ways of targeting glutamate for migraine therapy.

Keywords: Aura; Cortical spreading depression; Glutamate; Headache; Migraine.

Conflict of interest statement

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Jan Hoffmann has consulted for and/or serves on an advisory board of Allergan, Autonomic Technologies Inc., Chordate Medical AB, Novartis, and Teva. He received honoraria for speaking from Allergan, Chordate Medical AB, Novartis, and Teva. Andrew Charles has served as a consultant for Amgen, Alder, Biohaven, Eli Lilly, and eNeura. He has received grant funding from Takeda Pharmaceuticals.

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