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) in December 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. But unfortunately due to unknown reasons this product is hardly available in Germany if at all.

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 ]

In the US, Relpax is marketed by Viatris after Upjohn was spun off from Pfizer. [10] [11] [12]

Related Research Articles

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

Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor. It is used for acute migraines, sometimes with caffeine as the combination ergotamine/caffeine.

<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

Rizatriptan, sold under the brand name Maxalt among others, is a medication used for the treatment of migraine headaches. It is taken by mouth. It can also be applied on the tongue. It is a serotonin (5-HT) 1B/1D receptor agonist (triptan).

<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 serotonergic medication which is used in the acute treatment of migraine attacks with or without aura and cluster headaches. It is taken by mouth as a swallowed or disintegrating tablet or as a nasal spray.

<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.

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

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and as an antimigraine agent in the treatment of migraine headaches. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

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

Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the market in the United States and Canada due to safety concerns. It is taken by mouth.

<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">Nicergoline</span> Chemical compound

Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

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

Naratriptan (trade names include Amerge) is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. It is a selective 5-HT1 receptor subtype agonist.

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

5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.

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

5-hydroxytryptamine (serotonin) receptor 1F, also known as HTR1F is a 5-HT1 receptor protein and also denotes the human gene encoding it.

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

The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP) and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels. This receptor has been a drug development target for the treatment of several clinical disorders. The 5-HT7 receptor is encoded by the HTR7 gene, which in humans is transcribed into 3 different splice variants.

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

5-Carboxamidotryptamine (5-CT) is a tryptamine derivative closely related to the neurotransmitter serotonin.

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They are selective 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D) agonists. Migraine is a complex disease which affects about 15% of the population and can be highly disabling. Triptans have advantages over ergotamine and dihydroergotamine, such as selective pharmacology, well established safety record and evidence-based prescribing instructions. Triptans are therefore often preferred treatment in migraine.

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

Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.

<span class="mw-page-title-main">PNU-181731</span> Chemical compound

PNU-181731 is a drug which acts as an agonist at serotonin 5-HT2 receptors, with strongest binding affinity for the 5-HT2C subtype at 4.8nM, and weaker 5-HT2A affinity of 18nM. It has anxiolytic effects in animal studies with around one tenth the potency of alprazolam and no significant ataxia or other side effects noted.

<span class="mw-page-title-main">PHA-57378</span> Chemical compound

PHA-57378 is a drug which acts as an agonist at serotonin 5-HT2 receptors, having a binding affinity of 4.1 nM at the 5-HT2A subtype and 4.3 nM at 5-HT2C. It has anxiolytic effects in animal studies.

<span class="mw-page-title-main">MPMI (drug)</span> Chemical compound

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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, et al. (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, 13 August 1996.
  7. ↑ U.S. Patent no. 6110940 , Valerie Denise Harding, et al., Salts of an anti-migraine indole derivative, 29 August 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.
  10. ↑ "Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan". Pfizer. 16 November 2020. Retrieved 17 June 2024– via Business Wire.
  11. ↑ "Relpax". Pfizer. Retrieved 17 June 2024.
  12. ↑ "Brands". Viatris. 16 November 2020. Retrieved 17 June 2024.
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