Therapeutic potential of novel glutamate receptor antagonists in migraine

Background: Migraine is a common and disabling neurological disorder. Although the pharmacotherapy of migraine has advanced in parallel with our understanding of the pathophysiology of the disease, there is still a considerable unmet need to find more effective treatments. Migraine pathophysiology involves activation or the perception of activation of the trigeminovascular system. Glutamate, the major excitatory neurotransmitter in the CNS, is implicated in elements of the pathophysiology of the disorder, including trigeminovascular activation, central sensitization and cortical spreading depression. Objective: The aim of this article is to review the potential use of glutamate receptor antagonists as innovative neuronally targeted treatments of migraine. Methods: A systematic search of peer-reviewed publications was performed in PubMed on glutamate and migraine/trigeminovascular activation, and important references providing an insight into migraine pathophysiology are included. The results of unpublished trials were obtained from presentations at national and international meetings. Results/conclusions: The preclinical and clinical data argue strongly for a role of glutamatergic receptor activation in migraine. The pharmacology of glutamatergic trigeminovascular responses in brain areas involved in migraine pathophysiology is relevant to the development of new therapies for this disabling condition. Glutamate receptors represent a promising target for a valuable, non-vasoconstrictor, and perhaps more importantly neuronal-specific therapeutic approach to the treatment of migraine.