The mode of action of sumatriptan is vascular? A debate.
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 arterio-venous 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.
Humphrey
P P
PP
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, UK.
Goadsby
P J
PJ
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006801:Humans; D008881:Migraine Disorders / Q000209:etiology* / Q000503:physiopathology; D009411:Nerve Endings / Q000187:drug effects*; D018170:Sumatriptan / Q000494:pharmacology*; D014276:Trigeminal Nerve / Q000187:drug effects*
D018170:Sumatriptan