5-HT(1)-like receptor agonists and the pathophysiology of migraine

Recently, AG-25086 and GR-43175 have been reported to be highly effective in aborting acute migraine attacks. These compounds seem selectively to stimulate a sub-population of 5-HT(1)-like receptors to inhibit noradrenaline release from certain sympathetic neurovascular terminals, to contract dog saphenous vein and dog, monkey and human basilar arteries, and to decrease the arteriovenous anastomotic component of carotid blood flow in the cat. GR-43175 neither has any antinociceptive effect nor crosses the blood-brain barrier. Pramod Saxena and Michel Ferrari review the clinical effectiveness of these 5-HT(1)-like receptor agonists and their selective pharmacology, both of which strongly suggest that excessive dilatation in the extracerebral cranial (scalp and/or dural) vasculature is an integral part of the pathophysiology of migraine.