Triptans are a class of medications used in the treatment of migraine headaches. Triptans act as antimigraine agents by selectively binding to the serotonin receptors 5-HT1B and 5-HT1D. Triptan binding to the vascular 5-HT1B receptors leads to vasoconstriction of the cranial arteries, which painfully dilate during a migraine attack. Naratriptan is a selective 5-HT1B/1D receptor agonist and leads to vasoconstriction in the basilar artery and the blood vessels of the dura mater. It decreases peripheral nociception either by selective cranial vasoconstriction or an effect on trigeminovascular nerves. The blocking effect of sumatriptan indicated a peripheral effect on trigeminal vascular nerves in neurogenically mediated plasma extravasation. Naratriptan has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.

Naratriptan Mechanism of Action pathway References