Glutamate receptor antagonists in the management of migraine

Drugs. 2014 Jul;74(11):1165-76. doi: 10.1007/s40265-014-0262-0.


Migraine is a neurovascular disorder that is associated with severe headache and neurologic symptoms. The pathogenesis of migraine is believed to involve trigeminovascular system activation with the primary dysfunction located in brainstem. Glutamate, the major excitatory neurotransmitter in the central nervous system, and its receptors have since long been suggested in migraine pathophysiology. Different preclinical studies have confirmed their potential role in migraine. Moreover, several glutamate receptor modulators have been studied in clinical studies, some with promising results. In this review, we will give an overview of what is known about the role of glutamate in the pathogenesis of migraine, which will be followed by an overview of available efficacy, safety and tolerability data for glutamate receptor inhibitors in clinical development for the treatment of migraine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic / methods
  • Disease Management
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Humans
  • Isoquinolines / pharmacology
  • Isoquinolines / therapeutic use
  • Migraine Disorders / diagnosis
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / metabolism
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Receptors, Glutamate* / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use


  • Excitatory Amino Acid Antagonists
  • Isoquinolines
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Tetrazoles
  • tezampanel