Sumatriptan

Class

• Triptan sulfa serotonin (5HT1) agonist

Indications

• Migraine headaches with or without aura

Administration/Absorption

• Oral

  • Poor availability due to presystemic metabolism

• Subcutaneous injection

• Nasal spray

Dosage

Distribution

• Volume of distribution 2.7 L/kg [subcutaneous dosing]

Mechanism

• Selective agonist of vascular serotonin ((5-hydroxytryptamine; 5-HT) type 1-like receptors, likely the 5-HT1D and 5-HT1B subtypes

  • The 5-HT1B and 5-HT1D receptors function as autoreceptors

  • Adenylate cyclase activity is inhibited via regulatory G proteins; increases intracellular calcium, and affects other intracellular events

  • Inhibits the firing of serotonin neurons and cause a reduction in the synthesis and release of serotonin upon activation

• Has no significant affinity or pharmacological activity at:

  • 5-HT2, 5-HT3 receptor subtypes

  • Alpha1-, alpha2-, or beta-adrenergic receptors

  • Dopamine1 or 2 receptors

  • Muscarinic receptors

  • Benzodiazepine receptors

• This results in vasoconstriction and inhibtion of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release.

Excretion

• Hepatic metabolism

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

• 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

• Half-life 2.5 hrs

Side effects

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

Interactions

Contraindications