Eletriptan: Difference between revisions

{{Short description|Chemical compound}}

| Watchedfields = changed

| verifiedrevid = 459434734

| image = Eletriptan skeletal.svg

| image2 = Eletriptan 3D ball-and-stick.png

| tradename = Relpax, Relert

| Drugs.com = {{drugs.com|monograph|eletriptan-hydrobromide}}

| DailyMedID = Eletriptan

| pregnancy_AU = B1

| pregnancy_US = C

| routes_of_administration = [[Oral administration|By mouth]]

| ATC_prefix = N02

| ATC_suffix = CC06

| ATC_supplemental =

| legal_AU = S4

| legal_CA = Rx-only

| legal_UK = POM

| legal_UK_comment = <ref name="Relpax SmPC">{{cite web | title=Relpax 20mg Film-Coated Tablets. - Summary of Product Characteristics (SmPC) | website=(emc) | date=3 July 2020 | url=https://www.medicines.org.uk/emc/product/1568/smpc | access-date=11 November 2020}}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Relpax FDA label">{{cite web | title=Relpax- eletriptan hydrobromide tablet, film coated | website=DailyMed | date=10 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=986dc112-b97b-44a3-bfaf-074f906f8bb2 | access-date=11 November 2020}}</ref>

| legal_status = Rx-only

| metabolism = [[CYP3A4]]

| excretion =

| index2_label = HBr

| CAS_number2_Ref = {{cascite|correct|??}}

| CAS_number2 = 177834-92-3

| PubChem2 = 656631

| IUPHAR_ligand = 40

| DrugBank2_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank2 = DBSALT000884

| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID2 = 570985

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = M41W832TA3

| KEGG = D07887

| KEGG2_Ref = {{keggcite|changed|kegg}}

| KEGG2 = D01973

| ChEBI2_Ref = {{ebicite|correct|EBI}}

| ChEBI2 = 61176

| ChEMBL2_Ref = {{ebicite|correct|EBI}}

| ChEMBL2 = 1201003

| IUPAC_name = 3-{[(2''R'')-1-methylpyrrolidin-2-yl]methyl}-5-[2-(benzenesulfonyl)ethyl]-1''H''-indole

| C=22 | H=26 | N=2 | O=2 | S=1

| smiles = CN1CCC[C@@H]1Cc3c[nH]c4ccc(CCS(=O)(=O)c2ccccc2)cc34

| StdInChI = 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

'''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]] [[headache]]s.<ref name="pmid25624770">{{cite journal | vauthors = Bhambri R, Mardekian J, Liu LZ, Schweizer E, Ramos E | title = A review of the pharmacoeconomics of eletriptan for the acute treatment of migraine | journal = International Journal of General Medicine | volume = 8 | issue = | pages = 27–36 | date = 2015 | pmid = 25624770 | pmc = 4296958 | doi = 10.2147/IJGM.S73673 | doi-access = free }}</ref><ref name="pmid27582896">{{cite journal | vauthors = Capi M, Curto M, Lionetto L, de Andrés F, Gentile G, Negro A, Martelletti P | title = Eletriptan in the management of acute migraine: an update on the evidence for efficacy, safety, and consistent response | journal = Therapeutic Advances in Neurological Disorders | volume = 9 | issue = 5 | pages = 414–23 | date = September 2016 | pmid = 27582896 | pmc = 4994780 | doi = 10.1177/1756285616650619 }}</ref> It is used as an [[abortive medication]], blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by [[Pfizer|Pfizer Inc]].

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 (symptom)|aura]] in adults.<ref name=accessdata>{{cite web | title=Drug Approval Package: Relpax (Eletriptan) NDA #021016 | website=U.S. [[Food and Drug Administration]] (FDA) | date=4 April 2002 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21016_Relpax.cfm | access-date=11 November 2020}}</ref> It is available only by [[Medical prescription|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&nbsp;mg and 40&nbsp;mg strengths.

Eletriptan was covered by {{US patent|5545644|U.S. Patent no. 5545644}}<ref name=accessdata/><ref>{{US patent|5545644|U.S. Patent no. 5545644}}, John E. Macor & Martin J. Wythes, ''Indole Derivatives'', August 13, 1996.</ref> and {{US patent|6110940|U.S. Patent no. 6110940}};<ref name=accessdata/><ref>{{US patent|6110940|U.S. Patent no. 6110940}}, Valerie Denise Harding, ''et al.'', ''Salts of an anti-migraine indole derivative'', August 29, 2000.</ref> both now expired.

{{further|Serotonin receptor agonist|Triptan#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 receptor|5-HT₁ family receptor]]s. Eletriptan binds with high affinity to the [[5-HT1B|5-HT_[1B]]_, [[5-HT1D|_1D]]_, [[5-HT1F|_1F]]] receptors. It has a modest affinity to the [[5-HT1A|5-HT_[1A]]_, [[5-HT1E|_1E]]_, [[5-HT2B receptor|_2B]]_, [[5-HT7|_7]]] receptors, and little to no affinity at the [[5-HT2A|5-HT_[2A]]_, [[5-HT2C receptor|_2C]]_, [[5-HT3|₃]]_, [[5-HT4|₄]]_, [[5-HT5A|_5A]]_, [[5-HT6|_6]]] receptors.

Eletriptan has no significant affinity or pharmacological activity at [[adrenergic receptor|adrenergic]] [[alpha-1 adrenergic receptor|α₁]], [[alpha-2 adrenergic receptor|α₂]], or [[beta-adrenergic receptor|β]]; [[dopamine receptor|dopaminergic]] [[D1 receptor|D₁]] or [[D2 receptor|D₂]]; [[muscarinic acetylcholine receptor|muscarinic]]; or [[opioid receptor]]s. 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.<ref name="AC">{{cite book|title=Austria-Codex| veditors = Jasek W |publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=62nd|isbn=978-3-85200-181-4|pages=6984–8|language=German}}</ref>

==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 5HT_1B 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]].<ref name="AC" />

==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 alkaloid]]s, such as [[dihydroergotamine]], add to the drug's hypertensive effect and should be separated by at least 24 hours.<ref name="AC" />

==Additional chemical names==

* 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

== Society and culture ==

=== Brand names ===

It is sold in the United States, Canada, Australia, and the United Kingdom under the brand name Relpax,<ref name="Relpax FDA label" /><ref>{{cite web | title=Relpax Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=74152 | access-date=11 November 2020}}</ref><ref name="Relpax SmPC" /> and in several other countries under the brand name Relert.{{cn|date=October 2020}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/143322-58-1 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Eletriptan }}

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/177834-92-3 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Eletriptan hydrobromide }}

{{Serotonin receptor modulators}}

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[[Category:5-HT1D agonists]]

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[[Category:Drugs developed by Pfizer]]

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