title: Current and prospective pharmacological targets in relation to antimigraine action.
abstract: Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, alpha-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT(1B/1D) receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT(2) receptor antagonists, Ca(2+) channel blockers, and beta-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT(1-7)), adrenergic (alpha(1), alpha(2,) and beta), calcitonin gene-related peptide (CGRP(1) and CGRP(2)), adenosine (A(1), A(2), and A(3)), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon.
authors.affiliation: Division of Vascular Pharmacology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Suneet
authors.initials: S
authors.lastname: Mehrotra
authors.forename: Saurabh
authors.initials: S
authors.lastname: Gupta
authors.forename: Kayi Y
authors.initials: KY
authors.lastname: Chan
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: David
authors.initials: D
authors.lastname: Centurión
authors.forename: Pramod R
authors.initials: PR
authors.lastname: Saxena
authors.forename: Antoinette
authors.initials: A
authors.lastname: MaassenVanDenBrink
mesh_terms: D000322:Adrenergic Agonists / Q000627:therapeutic use; D018674:Adrenergic Antagonists / Q000627:therapeutic use; D000818:Animals; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D004358:Drug Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D008954:Models, Biological; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists