Eletriptan

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Eletriptan
Eletriptan skeletal.svg
Eletriptan 3D ball-and-stick.png
Clinical data
Trade names Relpax, Relert
AHFS/Drugs.com Monograph
MedlinePlus a603029
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 50%
Metabolism CYP3A4
Elimination half-life 4 hours
Identifiers
  • 3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-5-[2-(benzenesulfonyl)ethyl]-1H-indole
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.167.337 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H26N2O2S
Molar mass 382.52 g·mol−1
3D model (JSmol)
  • CN1CCC[C@@H]1Cc3c[nH]c4ccc(CCS(=O)(=O)c2ccccc2)cc34
  • InChI=1S/C22H26N2O2S/c1-24-12-5-6-19(24)15-18-16-23-22-10-9-17(14-21(18)22)11-13-27(25,26)20-7-3-2-4-8-20/h2-4,7-10,14,16,19,23H,5-6,11-137T56T X mark.svgN
  • Key:PWVXXGRKLHYWKM-LJQANCHMSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second-generation triptan medication intended for treatment of migraine headaches. [3] [4] It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc.

Contents

Approval and availability

Eletriptan was approved by the US Food and Drug Administration (FDA) on December 26, 2002, for the acute treatment of migraine with or without aura in adults. [5] 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 [5] [6] and U.S. Patent no. 6110940 ; [5] [7] 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-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.

Side effects

Common side effects include hypertension, tachycardia, headache, dizziness, drowsiness and symptoms similar to angina pectoris. Severe allergic reactions are rare. [8]

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. [8]

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. [8]

Additional chemical names

Society and culture

Brand names

It is sold in the United States, Canada, Australia, and the United Kingdom under the brand name Relpax, [2] [9] [1] and in several other countries under the brand name Relert.[ citation needed ]

Related Research Articles

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<span class="mw-page-title-main">Ergotamine</span> Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand names Cafergot and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor.

<span class="mw-page-title-main">Triptan</span> Class of pharmaceutical drugs

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.

<span class="mw-page-title-main">Rizatriptan</span> Medication used for the treatment of migraine headaches

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<span class="mw-page-title-main">Zolmitriptan</span> Medication used in treatment of migraines

Zolmitriptan, sold under the brand name Zomig among others, is a triptan used in the acute treatment of migraine attacks with or without aura and cluster headaches. It is a selective serotonin receptor agonist of the 1B and 1D subtypes.

<span class="mw-page-title-main">Dihydroergotamine</span> An ergot alkaloid used to treat migraines

Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. Nausea is a common side effect.

Caffeine/ergotamine is the proprietary name of a medication consisting of ergotamine tartrate and caffeine. This combination is used for the treatment of headaches, such as migraine headache.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

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<span class="mw-page-title-main">Methysergide</span> Chemical compound

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<span class="mw-page-title-main">Almotriptan</span> Chemical compound

Almotriptan is a triptan medication discovered and developed by Almirall for the treatment of heavy migraine headache.

<span class="mw-page-title-main">Antimigraine drug</span> Medication intended to reduce the effects or intensity of migraine headache

Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks.

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5-HT<sub>1D</sub> receptor Serotonin receptor which affects locomotion and anxiety in humans

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5-HT<sub>1F</sub> receptor Protein-coding gene in the species Homo sapiens

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5-HT<sub>7</sub> receptor Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">5-Carboxamidotryptamine</span> Chemical compound

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<span class="mw-page-title-main">Substituted tryptamine</span> Class of indoles

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<span class="mw-page-title-main">CP-122,288</span> Chemical compound

CP-122,288 is a drug which acts as a potent and selective agonist for the 5-HT1B, 5-HT1D and 5-HT1F serotonin receptor subtypes. It is a derivative of the migraine medication sumatriptan, but while CP-122,288 is 40,000 times more potent than sumatriptan as an inhibitor of neurogenic inflammation and plasma protein extravasation, it is only twice as potent as a constrictor of blood vessels. In human trials, CP-122,288 was not found to be effective as a treatment for migraine, but its selectivity for neurogenic anti-inflammatory action over vasoconstriction has made it useful for research into the underlying causes of migraine.

References

  1. 1 2 "Relpax 20mg Film-Coated Tablets. - Summary of Product Characteristics (SmPC)". (emc). 3 July 2020. Retrieved 11 November 2020.
  2. 1 2 "Relpax- eletriptan hydrobromide tablet, film coated". DailyMed. 10 December 2019. Retrieved 11 November 2020.
  3. ↑ Bhambri R, Mardekian J, Liu LZ, Schweizer E, Ramos E (2015). "A review of the pharmacoeconomics of eletriptan for the acute treatment of migraine". International Journal of General Medicine. 8: 27–36. doi: 10.2147/IJGM.S73673 . PMC   4296958 . PMID   25624770.
  4. ↑ Capi M, Curto M, Lionetto L, de Andrés F, Gentile G, Negro A, Martelletti P (September 2016). "Eletriptan in the management of acute migraine: an update on the evidence for efficacy, safety, and consistent response". Therapeutic Advances in Neurological Disorders. 9 (5): 414–23. doi:10.1177/1756285616650619. PMC   4994780 . PMID   27582896.
  5. 1 2 3 "Drug Approval Package: Relpax (Eletriptan) NDA #021016". U.S. Food and Drug Administration (FDA). 4 April 2002. Retrieved 11 November 2020.
  6. ↑ U.S. Patent no. 5545644 , John E. Macor & Martin J. Wythes, Indole Derivatives, August 13, 1996.
  7. ↑ U.S. Patent no. 6110940 , Valerie Denise Harding, et al., Salts of an anti-migraine indole derivative, August 29, 2000.
  8. 1 2 3 Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 6984–8. ISBN   978-3-85200-181-4.
  9. ↑ "Relpax Product information". Health Canada. 25 April 2012. Retrieved 11 November 2020.
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