{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 447824430 | image = Avanafil.svg | image_class = skin-invert-image | alt = | image2 = Avanafil ball-and-stick.png | image_class2 = bg-transparent | alt2 = | caption = Avanafil is a PDE5 inhibitor
<!--Clinical data-->| tradename = Stendra | Drugs.com = {{drugs.com|monograph|avanafil}} | MedlinePlus = a614010 | licence_EU = yes | DailyMedID = Avanafil | licence_US = Avanafil | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = | routes_of_administration = By mouth | ATC_prefix = G04 | ATC_suffix = BE10 | legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2016 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2016 | access-date=10 April 2023}}</ref> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = POM | legal_US = Rx-only | legal_EU = Rx-only
<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 330784-47-9 | PubChem = 9869929 | IUPHAR_ligand = 7448 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB06237 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 8045620 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = DR5S136IVO | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D03217 | ChEBI = 66876 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1963681 | NIAID_ChemDB = | PDB_ligand = E6L | synonyms = <!--Chemical data--> | IUPAC_name = (''S'')-4-((3-chloro-4-methoxybenzyl)amino)-2-(2-(hydroxymethyl)pyrrolidin-1-yl)-''N''-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide | C = 23 | H = 26 | Cl = 1 | N = 7 | O = 3 | smiles = Clc1c(OC)ccc(c1)CNc3nc(ncc3C(=O)NCc2ncccn2)N4[C@@H](CCC4)CO | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C23H26ClN7O3/c1-34-19-6-5-15(10-18(19)24)11-27-21-17(22(33)28-13-20-25-7-3-8-26-20)12-29-23(30-21)31-9-2-4-16(31)14-32/h3,5-8,10,12,16,32H,2,4,9,11,13-14H2,1H3,(H,28,33)(H,27,29,30)/t16-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = WEAJZXNPAWBCOA-INIZCTEOSA-N }}
'''Avanafil''' is a PDE5 inhibitor approved for erectile dysfunction by the FDA on April 27, 2012<ref>{{cite web |url=https://www.drugs.com/history/stendra.html |title=Stendra FDA Approval History |author=<!--Not stated--> |publisher=Drugs.com |access-date=6 March 2021}}</ref> and by EMA on June 21, 2013.<ref>{{cite web| url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002581/human_med_001661.jsp&mid=WC0b01ac058001d124| title=Spedra (avanafil)| publisher=European Medicines Agency| access-date=17 April 2014| archive-date=1 April 2014| archive-url=https://web.archive.org/web/20140401111423/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002581%2Fhuman_med_001661.jsp&mid=WC0b01ac058001d124| url-status=dead}}</ref> Avanafil is sold under the brand names '''Stendra''' and '''Spedra'''. It was invented at Mitsubishi Tanabe Pharma, formerly known as Tanabe Seiyaku Co.,<ref name = "US6797709" /> and licensed to Vivus Inc., which partnered with Menarini Group to commercialise Spedra in over forty European countries, Australia, and New Zealand.<ref>{{cite web | title = VIVUS Announces Avanafil Partnership With Menarini | publisher = Vivus Inc |url=http://ir.vivus.com/releasedetail.cfm?releaseid=775706 |archive-url=https://web.archive.org/web/20151208155146/http://ir.vivus.com/releasedetail.cfm?ReleaseID=775706 |archive-date=2015-12-08 |url-status=dead }}</ref> Metuchen Pharmaceuticals obtained exclusive rights within the United States.<ref>{{cite web | title = VIVUS and Metuchen Pharmaceuticals Announce License Agreement for Commercial Rights to Stendra | url = http://ir.vivus.com/news-releases/news-release-details/vivus-and-metuchen-pharmaceuticals-announce-license-agreement | archive-url = https://web.archive.org/web/20221129030618/http://ir.vivus.com/news-releases/news-release-details/vivus-and-metuchen-pharmaceuticals-announce-license-agreement | archive-date = 29 November 2022 | publisher = Vivus Inc | date = 3 October 2016 }}</ref>
Avanafil acts by inhibiting a specific phosphodiesterase type 5 enzyme found in various body tissues, primarily in the corpus cavernosum penis.<ref>{{cite web| url=http://www.medicinenet.com/avanafil_stendra/article.htm | publisher = Medicine Net | access-date = 17 April 2014 | title= avanafil, Spedra }}</ref> Other similar drugs are sildenafil, tadalafil and vardenafil. The advantage of avanafil is that it has very fast onset of action compared with other PDE5 inhibitors. It is absorbed quickly, reaching a maximum serum concentration in about thirty to forty-five minutes.<ref name="Kyle_2013">{{cite journal | vauthors = Kyle JA, Brown DA, Hill JK | title = Avanafil for erectile dysfunction | journal = The Annals of Pharmacotherapy | volume = 47 | issue = 10 | pages = 1312–1320 | date = October 2013 | pmid = 24259695 | doi = 10.1177/1060028013501989 | publisher = Sage Publishing | s2cid = 6562049 }}</ref> About two-thirds of the participants were able to engage in sexual activity within fifteen minutes.<ref name="Kyle_2013"/>
== Medical use == Avanafil is used to treat erectile dysfunction (ED).<ref name="pmid22973106">{{cite journal | vauthors = Burke RM, Evans JD | title = Avanafil for treatment of erectile dysfunction: review of its potential | journal = Vascular Health and Risk Management | volume = 8 | issue = | pages = 517–523 | date = 2012 | pmid = 22973106 | pmc = 3433322 | doi = 10.2147/VHRM.S26712 | doi-access = free }}</ref>
== Adverse effects == Although avanafil is generally well tolerated, dose dependent adverse effects can occur.<ref name="Kyle_2013" /> The most common adverse effects include headache, flushing, nasopharyngitis, nasal congestion, and back pain.<ref name="Kyle_2013" /> While it is also uncommon, there is a potential for visual disturbances to occur in patients,<ref name="Kyle_2013" /> as well as hearing impairment.<ref name="Zhang_2024">{{cite journal | vauthors = Zhang X, Xia L, Yang Q, Tang P | title=Phosphodiesterase type 5 inhibitors related hearing impairment: a real world study based on the FDA adverse event reporting system | journal=Scientific Reports | volume=14 | date=April 2024 | issn=2045-2322 | pmid=38679603 | pmc=11056362 | doi=10.1038/s41598-024-60493-w | url=https://www.nature.com/articles/s41598-024-60493-w | access-date=2025-12-08 | page=}}</ref>
== Mechanism of action == Avanafil inhibits phosphodiesterase-5, preventing the degradation of cGMP.<ref>{{cite journal | vauthors = Kotera J, Mochida H, Inoue H, Noto T, Fujishige K, Sasaki T, Kobayashi T, Kojima K, Yee S, Yamada Y, Kikkawa K, Omori K | display-authors = 6 | title = Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction | journal = The Journal of Urology | volume = 188 | issue = 2 | pages = 668–674 | date = August 2012 | pmid = 22704456 | doi = 10.1016/j.juro.2012.03.115 }}</ref><ref name="Sanford_2013">{{cite journal | vauthors = Sanford M | title = Avanafil: A Review of Its Use in Patients with Erectile Dysfunction | journal = Drugs & Aging | volume = 30 | issue = 10 | pages = 853–62 | date = October 2013 | pmid = 23955441 | doi = 10.1007/s40266-013-0112-x | s2cid = 23558269 }}</ref> The increased levels of cGMP causes vasodilation, resulting in an increased blood flow in the penis.<ref name="Sanford_2013" /> Avanafil's mechanism of action takes place once nitric oxide is released, in association with sexual stimulation.<ref name="Sanford_2013" />
==Synthesis== Avanafil can be synthesized from a benzylamine derivative and a pyrimidine derivative:<ref name = "US6797709">{{cite patent | country = US | number = 6797709 | inventor = Yamada K, Matsuki K, Omori K Kikkawa K | title = Aromatic nitrogen-containing 6-membered cyclic compounds | gdate = 11 December 2003 | assign1 = Tanabe Seiyaku Co }}</ref> :500px
== References == {{Reflist}}
== External links == * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/avanafil | archive-url = https://web.archive.org/web/20170123205947/https://druginfo.nlm.nih.gov/drugportal/name/Avanafil | url-status = dead | archive-date = January 23, 2017 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Avanafil }}
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Category:Hydroxymethyl compounds Category:Carboxamides Category:Chlorobenzene derivatives Category:PDE5 inhibitors Category:Phenol ethers Category:Aminopyrimidines Category:Pyrrolidines Category:Erectile dysfunction drugs Category:Enones