indication

For the acute treatment of migraine attacks with or without aura in adults.

pharmacology

Naratriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonist. Naratriptan has only a weak affinity for 5-HT_1A, 5-HT_5A, 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. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Naratriptan also activates 5-HT₁ receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Naratriptan in humans.

mechanism of action

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.

toxicity

Symptoms of overdose include light-headedness, loss of coordination, tension in the neck, and tiredness.

biotransformation

Primarily hepatic. In vitro, naratriptan is metabolized by a wide range of cytochrome P450 isoenzymes into a number of inactive metabolites.

absorption

Well absorbed (74% oral biovaility), absorption is rapid with peak plasma concentrations after 2-5 hours. The rate of absorption is slower during a migraine attack.

half life

5-8 hours

drug interactions

Citalopram: Increased risk of CNS adverse effects

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dihydroergotamine: Naratriptan, a serotonin 5-HT1D receptor agonists, may increase the vasoconstricting effect of dihydroergotamine. Concomitant use of these two agents within 24 hours is contraindicated.

Dihydroergotoxine: Possible severe and prolonged vasocontriction

Ergonovine: Possible severe and prolonged vasocontriction

Ergotamine: Possible severe and prolonged vasoconstriction.

Escitalopram: Increased risk of CNS adverse effects

Fluoxetine: Increased risk of CNS adverse effects

Fluvoxamine: Increased risk of CNS adverse effects

Isocarboxazid: The use of two serotonin modulators increases the risk of serotonin syndrome. Consider alternate therapy or monitor for signs and symptoms of serotonin syndrome.

Methylergonovine: Possible severe and prolonged vasocontriction

Methysergide: Possible severe and prolonged vasoconstriction.

Nefazodone: Increased risk of CNS adverse effects

Paroxetine: Increased risk of CNS adverse effects

Phenelzine: The use of two serotonin modulators increases the risk of serotonin syndrome. Consider alternate therapy or monitor for signs and symptoms of serotonin syndrome.

Sertraline: Increased risk of CNS adverse effects

Sibutramine: Increased risk of CNS adverse effects

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Vilazodone: Increased risk of serotonin syndrome

Zolmitriptan: Concomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and naratriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.