Potential mechanisms of prospective antimigraine drugs: a focus on vascular (side) effects.
Currently available drugs for the acute treatment of migraine, i.e. ergot alkaloids and triptans, are cranial vasoconstrictors. Although cranial vasoconstriction is likely to mediate-at least a part of-their therapeutic effects, this property also causes vascular side-effects. Indeed, the ergot alkaloids and the triptans have been reported to induce myocardial ischemia and stroke, albeit in extremely rare cases, and are contraindicated in patients with known cardiovascular risk factors. In view of these limitations, novel antimigraine drugs devoid of vascular (side) effects are being explored. Currently, calcitonin gene-related peptide (CGRP) receptor antagonists, which do not have direct vasoconstrictor effects, are under clinical development. Other classes of drugs, such as 5-HT(1F) receptor agonists, glutamate receptor antagonists, nitric oxide synthase inhibitors, VPAC/PAC receptor antagonists and gap junction modulators, have also been proposed as potential targets for acute antimigraine drugs. Although these prospective drugs do not directly induce vasoconstriction, they may well induce indirect vascular effects by inhibiting or otherwise modulating the responses to endogenous vasoactive substances. These indirect vascular effects might contribute to the therapeutic efficacy of the previously mentioned compounds, but may alternatively also lead to vascular side-effects. As described in the current review, some of the prospective antimigraine drugs with a proposed non-vascular mechanism of action may still have direct or indirect vascular effects.
Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Kayi Y
KY
Chan
Steve
S
Vermeersch
Jan
J
de Hoon
Carlos M
CM
Villalón
Antoinette
A
Maassenvandenbrink
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004876:Ergot Alkaloids / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D014363:Tryptamines / Q000009:adverse effects / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004876:Ergot Alkaloids; D014363:Tryptamines; D014662:Vasoconstrictor Agents