indication

For the treatment of migraine attacks with or without aura.

pharmacology

Sumatriptan, an antimigraine drug, is a selective agonist of vascular serotonin ((5-hydroxytryptamine; 5-HT) type 1-like receptors, likely the 5-HT_1D and 5-HT_1B subtypes. It has no significant affinity (as measured using standard radioligand binding assays) or pharmacological activity at 5-HT2, 5-HT3 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic; dopamine1; dopamine2; muscarinic; or benzodiazepine receptors.

mechanism of action

The 5-HT_1B and 5-HT_1D receptors function as autoreceptors, which inhibit the firing of serotonin neurons and a reduction in the synthesis and release of serotonin upon activation. After sumatriptan binds to these receptors, adenylate cyclase activity is inhibited via regulatory G proteins, incrases intracellular calcium, and affects other intracellular events. This results in vasoconstriction and inhibtion of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release.

toxicity

Symptoms of overdose include convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation.

biotransformation

Hepatic. In vitro studies with human microsomes suggest that sumatriptan is metabolized by monoamine oxidase (MAO), predominantly the A isoenzyme.

absorption

Approximately 15%

half life

2.5 hours

route of elimination

Only 3% of the dose is excreted in the urine as unchanged sumatriptan; 42% of the dose is excreted as the major metabolite, the indole acetic acid analogue of sumatriptan.

drug interactions

Citalopram: Increased risk of CNS adverse effects

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

Dihydroergotamine: Possible severe and prolonged vasoconstriction

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 MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, sumatriptan. Concomitant therapy is contraindicated.

Lithium: Possible serotoninergic syndrome with this combination

Methysergide: Possible severe and prolonged vasoconstriction

Nefazodone: Increased risk of CNS adverse effects

Paroxetine: Increased risk of CNS adverse effects

Phenelzine: The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, sumatriptan. Concomitant therapy is contraindicated.

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

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Sumatriptan. Risk of serotonin syndrome and Sumatriptan toxicity. Concomitant therapy should be avoided.

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 sumatriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.