Siagran Mechanism of Action

Pharmacology: Pharmacodynamics: Sumatriptan is a selective 5-hydroxytryptamine₁ serotonin (5-HT₁ or serotonin) receptors agonist, particularly the 5-HT_1D (also called 5HT_1Dα) and 5-HT_1B (also called 5HT_1Dβ) subtypes on intracranial blood vessels that become dilated during a migraine attack and on sensory nerves of the trigeminal system. Sumatriptan has the highest affinity for the 5-HT_1D receptor, the most common serotonin receptor subtype in the brain, and a 2- to 17-fold lower affinity for 5-HT_1A receptors. Sumatriptan has essentially no affinity at other serotonin receptors (eg. 5-HT_2-4) or at receptors of the dopamine1, dopamine2, muscarinic, histamine, benzodiazepine, alpha-adrenergic and beta-adrenergic receptors.
Sumatriptan activates 5-HT_1D and 5-HT_1B to result in cranial vessel constriction, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway correlating with relief of migraine.
Pharmacokinetics: Absorption: Sumatriptan is rapidly absorbed. The bioavailability is about 14-15% because of incomplete absorption and presystemic metabolism. After a single 50 mg oral dose, peak plasma Sumatriptan concentrations averaged 31 ng/mL at 0.5-3 hours, while a single 100 mg oral dose of Sumatriptan produced peak plasma drug concentrations averaging 51 ng/mL approximately 2-2.5 hours. The onset of action of Sumatriptan in patients with migraine headaches correlates well with peak plasma drug concentrations. Plasma Sumatriptan concentrations associated with therapeutic effects in patients with migraine have ranged from 18-60 ng/mL. Onset of relief of migraine symptoms occurs about 30 minutes, maximum pain relief attained within 3-6 hours.
Food has no significant effect on oral 5-HT₁ agonist bioavailability, but delays Sumatriptan's T_max by approximately 30 minutes.
Distribution: Sumatriptan is approximately 14-21% bound to plasma proteins. The volume of distribution is 2.4 L/kg.
Metabolism: Sumatriptan is metabolized in the liver via monoamine oxidase (MAO) isoenzyme, principally the A isoenzyme (MAO-A); extensive first-pass metabolism following oral administration. The major metabolite of Sumatriptan is its inactive indole acetic acid analog eliminated in urine.
Elimination: The elimination half-life is approximately 2 hours. Sumatriptan is excreted in urine via glomerular filtration and tubular secretion about 57-60% of total dose; mostly as indole acetic acid metabolite and 3% of total dose as unchanged drug. Renal plasma clearance accounts for only 22% of the systemic clearance of 1,176-1,200 mL/min. Furthermore Sumatriptan is excreted in feces about 37-40%.