Eletriptan

Absorption

Well absorbed after oral administration with a mean absolute bioavailability of approximately 50%.

Toxicity

Based on the pharmacology of the 5-HT1B/1D agonists, hypertension or other more serious cardiovascular symptoms could occur on overdose.

Description

Eletriptan, the seventh member of the triptan class of antimigraine drugs was launched in Switzerland for the acute treatment of migraine. The 5-step synthesis of this conformationally restricted analog of sumatriptan involves the deprotonation of 5- bromoindole with Grignard reagent at the position C3 followed by a condensation with NCbz- D-proline acid chloride to afford the key Cbz-D-prolyl intermediate. After reduction with LiAIH4, the sulfone moiety was introduced in postion 5 by a palladium cross-coupling Heck reaction using the phenylvinyl sulfone. Eletriptan is a 5-HT receptor agonist that binds to 5-HT_1B, 5HT_1D and 5HT_1F receptors with high potency. Activation of these receptors causes constriction of extracerebral intracranial vessels, abolition of the dural extravasation and neurogenic inflammation, and inhibition of trigeminal neuronal discharge. Eletriptan was found to be the most potent agonist at the 5-HT_1D receptor compared to the other triptans with pEC₅₀ value of 9.2. In thousands of participants in clinical trials, eletriptan has acted more effectively and more rapidly than sumatriptan to relieve pain from mild to severe attacks of migraine. Eletriptan also reduced time lost for ordinary activity to patients with migraine attacks when compared to placebo and when compared to sumatriptan. Eletriptan was also superior to sumatriptan in terms of relieving functional disability, nausea, photophobia and phonophobia. Unlike other compounds of its class, eletriptan has a positive logD value, that could underlie its rapid and complete oral absorption and may be suggestive of a good brain penetration. The oral biovailability of Eletriptan is approximately 50% (14% for Sumatriptan) with a half life of 5.7h (2h for Sumatriptan). Eletriptan was well tolerated with mild to moderate adverse events including asthenia, somnolence, dizziness and nausea. Eletriptan is a new potent and fast-acting triptan for the treatment of migraine attacks.

The Uses of Eletriptan

Eletriptan is a selective serotonin 5-HT1B and 5-HT1D receptor agonist and used to treat migraines (1,2,3).

Indications

For the acute treatment of migraine with or without aura in adults.

Background

Eletriptan is a second generation triptan drug developed by Pfizer Inc for the treatment of migraine headaches.

Pharmacokinetics

Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist. In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat.

Metabolism

In vitro studies indicate that eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4. The N-demethylated metabolite of eletriptan is the only known active metabolite.