Eletriptan

Eletriptan (trade name Relpax, used in the form of eletriptan hydrobromide) is a second generation triptan drug intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc. It is sold in the US and Canada under the brand name Relpax, and in several other countries under the brand name Relert.

Eletriptan
Clinical data
Trade namesRelpax
AHFS/Drugs.comMonograph
MedlinePlusa603029
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration
    oral
    ATC code
    Legal status
    Legal status
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    Bioavailability50%
    MetabolismCYP3A4
    Elimination half-life4 hours
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.167.337
    Chemical and physical data
    FormulaC22H26N2O2S
    Molar mass382.52 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Approval and availability

    Eletriptan was approved by the U.S. Food and Drug Administration (FDA) on December 26, 2002, for the acute treatment of migraine with or without aura in adults.[1] It is available only by prescription in the United States and Canada. It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. It is available in 20 mg and 40 mg strengths.

    Eletriptan was covered by U.S. Patent no. 5545644[1][2] and U.S. Patent no. 6110940;[1][3] both now expired.

    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. 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-administrated 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.

    Side effects

    Common side effects include hypertension, tachycardia, headache, dizzyness, drowsiness and symptoms similar to angina pectoris. Severe allergic reactions are rare.[4]

    Contraindications

    Eletriptan is contraindicated in patients with various diseases of the heart and circulatory system, such as angina pectoris, severe hypertension, and heart failure, as well as in patients that have had a stroke or heart attack. This is due to the unusual side effect of coronary vasoconstriction due to serotonin 5HT1B antagonism, which can precipitate a heart attack in those already at risk. It is also contraindicated in severe renal or hepatic impairment due to its extensive liver metabolism through CYP3A4.[4]

    Interactions

    Strong inhibitors of the liver enzyme CYP3A4, such as erythromycin and ketoconazole, significantly increase blood plasma concentration of eletriptan and should be separated by at least 72 hours. Ergot alkaloids, such as dihydroergotamine, add to the drug's hypertensive effect and should be separated by at least 24 hours.[4]

    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

    References

    1. FDA AccessData entry for Eletriptan Hydrobromide, accessed March 10, 2010.
    2. U.S. Patent no. 5545644, John E. Macor & Martin J. Wythes, Indole Derivatives, August 13, 1996.
    3. U.S. Patent no. 6110940, Valerie Denise Harding, et al., Salts of an anti-migraine indole derivative, August 29, 2000.
    4. Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 6984–8. ISBN 978-3-85200-181-4.
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