The development of a highly selective 5‐HT₁ receptor agonist, sumatriptan, for the treatment of migraine

Abstract

Sumatriptan is a highly selective 5-HT1 receptor agonist and an effective treatment for migraine. It causes constriction of cranial blood vessels. In anaesthetised animals, it selectively constricts parts of the carotid vasculature and has been shown to inhibit plasma protein extravasation from blood vessels of the dura mater induced by antidromic stimulation of the trigeminal nerve. This effect may result from a localised vasoconstriction of the meningeal vessels and/or a direct inhibitory effect on adventitial nerve endings. Sumatriptan penetrates the blood brain barrier poorly. These findings are consistent with the view that the locus of action of sumatriptan is at the level of the wall of cranial blood vessels that are distended and edematous during a migraine headache. o 1992 Witey-Liss, tnc.

Suppression by the sumatriptan analogue, CP‐122,288 of c‐fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin

“…Moreover, traditional models do not assess the effects of drugs on nociception, but utilize measures of blood flow (Friberg, 1991;L'acombe et al, 1993), blood velocity (Zanette et al, 1992;Zwetsloot et al, 1992) or assess the ability of compounds to constrict or dilate vascular smooth muscle (Feniuk & Humphrey, 1992).…”

Agonistic and Antagonistic Bivalent Ligands for Serotonin and Dopamine Receptors Including their Transporters

“…These drugs are very effective for the treatment of migraine [6]. The pathophysiology of migraine is not completely understood, but dilation of cerebral blood vessels and hyperactivity of the trigeminal system seem to play a key role [7]. Both processes are mediated by serotonin agonism.…”

G-protein coupled receptors bivalent ligands and drug design

“…Among these, the 5-HT 1 subfamily has received considerable attention in the field of drug design and discovery. In particular, 5-HT 1B/1D receptor subtypes are under extensive investigations since the discovery that sumatriptan (37), a prototypic 5-HT 1B/1D agonist, is an effective drug for the treatment of acute attacks of migraine [57]. The implication of 5-HT 1B/1D receptor subtypes in migraine pathology has been confirmed by more recent results showing that other selective 5-HT 1B/1D agonists are also clinically effective in the treatment of migraine headache.…”