Mechanism of Action

Sumatriptan is an agonist for a vascular 5-hydroxytryptamine₁ receptor subtype (probably a member of the 5-HT_1D family) having only a weak affinity for 5-HT_1A, 5-HT_5A, and 5-HT₇ receptors and no significant affinity (as measured using standard radioligand binding assays) 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.

The vascular 5-HT₁ receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5-HT₁ receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may contribute to the antimigrainous effect of sumatriptan in humans.

In the anesthetized dog, sumatriptan selectively reduces the carotid arterial blood flow with little or no effect on arterial blood pressure or total peripheral resistance. In the cat, sumatriptan selectively constricts the carotid arteriovenous anastomoses while having little effect on blood flow or resistance in cerebral or extracerebral tissues. Pharmacokinetics

In a study of 20 female volunteers, the mean maximum concentration following a 5- and 20-mg intranasal dose was 5 and 16 ng/mL, respectively. The mean C_max following a 6-mg subcutaneous injection is 71 ng/mL (range, 49 to 110 ng/mL). The mean C_max is 18 ng/mL (range, 7 to 47 ng/mL) following oral dosing with 25 mg and 51 ng/mL (range, 28 to 100 ng/mL) following oral dosing with 100 mg of sumatriptan. In a study of 24 male volunteers, the bioavailability relative to subcutaneous injection was low, approximately 17%, primarily due to presystemic metabolism and partly due to incomplete absorption. Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated, but would be expected to be minor, given the low rate of protein binding. The mean volume of distribution after subcutaneous dosing is 2.7 L/kg and the total plasma clearance is approximately 1,200 mL/min.

The elimination half-life of sumatriptan administered as a nasal spray is approximately 2 hours, similar to the half-life seen after subcutaneous injection. 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.

Clinical and pharmacokinetic data indicate that administration of two 5-mg doses, 1 dose in each nostril, is equivalent to administration of a single 10-mg dose in 1 nostril.

Brand Name: Imitrex Nasal Spray
Generic Name: Sumatriptan

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