The mode of action of sumatriptan is vascular? A debate


  • This report is based on “The mode of action of sumatriptan is vascular’. A debate”, from the 2nd International Sumatriptan Symposium, held at Whistler, BC, Canada, on 11 September 1993 under the auspices of the Canadian Headache Society. Speakers’ remarks are paraphrased except when placed in quotation. Speaking for the motion was Professor Pat Humphrey from the Glaxo Institute of Applied Pharmacology at the University of Cambridge, UK, an eminent pharmacologist and leader of the team that discovered sumatriptan. Speaking against the motion was Dr Peter Goadsby, from the Faculty of Neurology at the University of New South Wales, and the Department of Neurology at the Prince Henry Hospital, Sydney, Australia. The Chairman, Dr KMA Welch, Professor of Neurology, Case Western Reserve University; and William T Gossett Chair of the Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA, encouraged the international audience of neurologists and headache specialists to join the debate and further discussion, as they would be asked to vote for or against the motion on conclusion of the debate.

Peter J Goadsby, Department of Neurology, The Prince Henry Hospital, Little Bay, Sydney, NSW 2036, Australia.


Two mechanisms have been proposed to explain the primary mode of action of sumatriptan: vasoconstriction, and trigeminal nerve terminal inhibition. Sumatriptan is a potent vasoconstrictor of intracranial arteries. It has been shown to increase blood flow velocity in large intracranial arteries in man in a dose-dependent fashion both during and between migraine attacks. Since the vasoconstrictor response of sumatriptan is reproducible outside the migraine attack, this action appears to be a direct vascular effect and not indirectly mediated via neural mechanisms. Sumatriptan also causes rapid constriction of dural and meningeal vessels in vivo. It does not modify cerebral blood flow but does constrict arteriovenous anastamoses that may be dilated during a migraine attack. This evidence suggests that sumatriptan has a direct, dose-related, vasoconstrictor action on certain intracranial blood vessels that correlates with its antimigraine activity. Alternatively, sumatriptan may act directly on the trigeminal sensory nerve terminals within the cranial blood vessel, inhibiting the release of sensory neuropeptides. Experimental data from animal studies have shown that following electrical stimulation of the trigeminal ganglion there is a neurogenic inflammatory response with plasma protein extravasation from dural blood vessels. This response can be significantly reduced by sumatriptan at a dose level similar to that used in clinical treatment. This finding is further supported by the clinical observation that sumatriptan reduces the plasma levels of calcitonin gene-related peptide which are raised during a migraine attack.