Eletriptan

Mechanism of action

Eletriptan is believed to reduce swelling of the blood vessels surrounding the brain. This swelling is associated with the head pain of a migraine attack. Eletriptan blocks the release of substances from nerve endings that cause more pain and other symptoms like nausea, and sensitivity to light and sound. It is thought that these actions contribute to relief of symptoms by eletriptan.

Eletriptan is a serotonin receptor agonist, specifically an agonist of certain 5-HT₁ family receptors.^[2] Eletriptan binds with high affinity to the 5-HT_{[1B, 1D, 1F]} receptors. It has a modest affinity to the 5-HT_{[1A, 1E, 2B, 7]} receptors, and little to no affinity at the 5-HT_{[2A, 2C, 3, 4, 5A, 6]} receptors.

Eletriptan has no significant affinity or pharmacological activity at adrenergic α₁, α₂, or β; dopaminergic D₁ or D₂; muscarinic; or opioid receptors. Eletriptan could be efficiently co-administered with nitric oxide synthase (NOS's) inhibitors for the treatment of NOS-dependent diseases (US patent US 2007/0254940).

Two theories have been proposed to explain the efficacy of 5-HT₁ receptor agonists in migraine. One theory suggests that activation of 5-HT₁ receptors located on intracranial blood vessels, including those on the arteriovenous anastomoses, leads to vasoconstriction, which is correlated with the relief of migraine headache. The other hypothesis suggests that activation of 5-HT₁ receptors on sensory nerve endings in the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

The drug is also notable in being a weak serotonin 5-HT_2A receptor agonist (EC₅₀Tooltip half-maximal effective concentration = 851 nM), albeit with about two to three orders of magnitude lower activational potency than at the serotonin 5-HT_1B and 5-HT_1D receptors.^[16]

Additional chemical names

• Merck Index: 3-[[(2R)-1-Methyl-2-pyrrolidinyl]methyl]-5-[2-(phenylsulfonyl)ethyl]-1H-indole
• 5-[2-(benzenesulfonyl)ethyl]-3-(1-methylpyrrolidin-2(R)-ylmethyl)-1H-indole
• (R)-5-[2-(phenylsulfonyl)ethyl]-3-[(1-methyl-2-pyrrolidinyl)methyl]-1H-indole

Brand names

Eletriptan is sold in the United States, Canada, Australia, and the United Kingdom under the brand name Relpax,^[2][25][1] and in several other countries under the brand name Relert.^{[citation needed]}

In the United States, Relpax is marketed by Viatris after Upjohn was spun off from Pfizer.^[26][27][28]