Sildenafil 32565 225798703 2008-07-15T13:28:11Z Edgar181 491706 {{sprotect2}} {{sprotect2}} {{Drugbox |IUPAC_name = <span style="white-space:nowrap;">1-[4-ethoxy-3-(6,7-dihydro-1-methyl-<br />7-oxo-3-propyl-1''H''-pyrazolo[4,3-''d'']pyrimidin-5-yl)<br />phenylsulfonyl]-4-methylpiperazine [[citrate]]</span> | image=Sildenafil-A-2D-skeletal.png | image2=Sildenafil-from-xtal-3D-balls.png | CAS_number=139755-83-2 | ATC_prefix=G04 | ATC_suffix=BE03 | PubChem=5281023 | DrugBank=APRD00556 | C=22|H=30|N=6|O=4|S=1 | molecular_weight = base: 474.6 g/mol | smiles = O=S(=O)(N1CCN(C)CC1)c4cc(C=2NC(=O)<BR>c3n(C)nc(CCC)c3N=2)c(OCC)cc4 | bioavailability= 40% | metabolism = [[liver|Hepatic]] | elimination_half-life = 3-4h | excretion = [[CYP3A4]] | pregnancy_category = N/A | legal_status = Rx-only | routes_of_administration=[[Wiktionary:oral|Oral]] }} {{dablink|"Viagra" redirects here. For the Russian/Ukrainian girl group also known as "Via Gra", see [[Nu Virgos]]}} '''Sildenafil citrate''', sold under the names '''Viagra''', '''Revatio''' and under various other names, is a [[Medication|drug]] used to treat male [[erectile dysfunction]] (impotence) and [[pulmonary hypertension|pulmonary arterial hypertension]] (PAH), developed by the [[pharmaceutical company]] [[Pfizer]]. Its primary competitors on the market are [[tadalafil]] (Cialis), and [[vardenafil]] (Levitra). ==History== Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizer's [[Sandwich, Kent]] research facility in England. It was initially studied for use in [[hypertension]] (high blood pressure) and [[angina pectoris]] (a symptom of [[ischaemic]] [[cardiovascular disease]]). The first clinical trials were conducted in [[Morriston Hospital]] in [[Swansea]].[http://www.abm.university-trust.wales.nhs.uk/page.cfm?orgId=743&pid=29457] Phase I [[clinical trial]]s under the direction of [[Ian Osterloh]] suggested that the drug had little effect on angina, but that it could induce marked penile [[erection]]s.<ref>{{cite journal | author=Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C | title=Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction | journal=Int J Impot Res | year=1996 | pages=47–52 | volume=8 | issue=2 | pmid=8858389}}</ref><ref>{{cite journal|author=Terrett NK ''et al''|title=Sildenafil (Viagra), a potent and selective inhibitor of Type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction|journal=Bioorg Med Chem Lett|year=1996|volume=6|pages=1819–1824 | doi = 10.1016/0960-894X(96)00323-X <!--Retrieved from CrossRef by DOI bot-->}}<!--not indexed on Medline--></ref> Pfizer therefore decided to market it for erectile dysfunction, rather than for angina. The drug was [[patent]]ed in [[1996]], approved for use in erectile dysfunction by the [[Food and Drug Administration]] on [[March 27]], [[1998]], becoming the first pill approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year.<ref>{{cite journal|author=Kling J|title=From hypertension to angina to Viagra|journal=Mod Drug Discov|year=1998|volume=1|pages=31–38|url=http://pubs.acs.org/hotartcl/mdd/98/novdec/viagra.html}}<!--Not indexed on PubMed--></ref> It soon became a great success: annual sales of Viagra in the period [[1999]]&ndash;[[2001]] exceeded $1 [[1000000000 (number)|billion]]. The British press portrayed Peter Dunn and Albert Wood as the inventors of the drug, a claim which Pfizer disputes.<ref name=bellis>{{cite web|author=Bellis M|url=http://inventors.about.com/library/weekly/aa013099.htm|title=Viagra, the patenting of an aphrodisiac|publisher=About.com}}</ref> Their names are on the manufacturing patent application drug, but Pfizer claims this is only for convenience. Even though sildenafil is available only by prescription from a doctor, it was advertised directly to consumers on U.S. TV (famously being endorsed by former [[United States Senate|United States Senator]] [[Bob Dole]] and [[Football (soccer)|soccer]] star [[Pelé]]). Numerous sites on the Internet offer Viagra for sale after an "online consultation," often a simple web questionnaire. The "Viagra" name has become so well known that many fake [[aphrodisiac]]s now call themselves "herbal Viagra" or are presented as blue tablets imitating the shape and colour of Pfizer's product. Viagra is also informally known as "Vitamin V", "the Blue Pill", as well as various other nicknames. In February 2007, it was announced that [[Boots the Chemist]] would trial [[Over-the-counter drug|over the counter]] sales of Viagra in stores in [[Manchester]], [[England]]. Men aged between 30 and 65 would be eligible to buy four tablets after a consultation with a [[pharmacist]].<ref>{{cite web|url=http://news.bbc.co.uk/1/hi/health/6351171.stm|title=Over-the-counter Viagra piloted|date=[[2007-02-11]]|publisher=British Broadcasting Corporation}}</ref> Pfizer's worldwide patents on sildenafil citrate will expire in 2011–2013. The [[United Kingdom|UK]] patent held by Pfizer on the use of [[PDE5 inhibitor]]s (see below) as treatment of impotence was invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002. ==Mechanism of action== Part of the physiological process of erection involves the [[parasympathetic nervous system]] causing the release of [[nitric oxide]] (NO) in the [[corpus cavernosum penis|corpus cavernosum]] of the penis. NO binds to the receptors of the enzyme [[guanylate cyclase]] which results in increased levels of [[cyclic guanosine monophosphate]] (cGMP), leading to [[smooth muscle]] relaxation (vasodilation) of the intimal cushions of the [[Helicine arteries of penis|helicine arteries]], resulting in increased inflow of blood and an erection. Sildenafil is a potent and selective inhibitor of [[cGMP specific phosphodiesterase type 5]] (PDE5) which is responsible for degradation of cGMP in the [[corpus cavernosum penis|corpus cavernosum]]. The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include [[tadalafil]] (Cialis) and [[vardenafil]] (Levitra). Sildenafil is [[metabolism|metabolised]] by [[liver|hepatic]] [[enzyme]]s and excreted by both the [[liver]] and [[kidney]]s. If taken with a high-fat meal, there may be a delay in absorption of sildenafil and the peak effect might be reduced slightly as the plasma concentration will be lowered. ==Dosage== [[Image:Viagra in Pack.jpg|right|thumb|200px|Viagra]] Viagra pills are blue and diamond-shaped with the words "Pfizer" engraved on one side, and "VGR xx" (where xx stands for "25", "50" or "100", the dose of that pill in milligrams) engraved on the other. The dose of sildenafil for erectile dysfunction is 25 mg to 100 mg taken not more than once per day between 30 minutes and 4 hours prior to [[sexual intercourse]]. It is usually recommended to start with a dosage of 50 mg (or even 25 mg) and then lower or raise the dosage as appropriate. The dosage for pulmonary arterial hypertension (Revatio) is one 20 mg tablet three times a day. Revatio pills are white, round, film-coated tablets imprinted with "RVT 20" on one side and "Pfizer" on the other. ==Market structure== In 2000, Viagra sales accounted for 92 percent of the global market for prescribed [[erectile dysfunction]] pills.<ref>[http://content.healthaffairs.org/cgi/reprint/19/2/147.pdf (pdf)]</ref> By 2007, Viagra's global share had plunged to about 50 percent due to entry of Cialis and Levitra, along with several other counterfeits and clones. ==Contraindications== [[Contraindications]] include: * When taking nitric oxide donors, organic nitrites and nitrates, such as [[glyceryl trinitrate]] (nitroglycerin), [[sodium nitroprusside]], [[amyl nitrite]] ("[[poppers]]")<ref>{{cite journal | author=Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM | title=ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association | journal=Journal of the American College of Cardiology | year=1999 | pages=273–82 | volume=33 | issue=1 | pmid=9935041 | doi=10.1016/S0735-1097(98)00656-1}}</ref> * In men for whom [[sexual intercourse]] is inadvisable due to [[cardiovascular]] risk factors * Severe [[Chronic liver disease|hepatic impairment]] (decreased liver function) * Severe impairment in [[renal function]] * [[Hypotension]] (low blood pressure) * Recent [[stroke]] or [[myocardial infarction|heart attack]] * Hereditary degenerative [[retinal disorders]] (including genetic disorders of retinal [[phosphodiesterase]]s) ==Side effects== Amongst sildenafil's rare but serious adverse effects are: [[priapism]], severe [[hypotension]], [[myocardial infarction]], [[ventricular tachycardia|ventricular arrhythmia]]s, [[stroke]] and increased [[intraocular pressure]].{{Fact|date=December 2007}} Common side effects include [[Sneeze|sneezing]], [[headache]], [[Flushing (physiology)|flushing]], [[dyspepsia]], [[palpitation]]s and [[photophobia]]. Care should be exercised by patients who are also taking [[Protease inhibitor (pharmacology)|Protease inhibitors]] for the treatment of [[HIV]]. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying the plasma levels of sildenafil, increasing the incidence and severity of side-effects. It is recommended that patients using protease inhibitors limit their use of sildenafil to no more than one 25-mg dose every 48 hours.{{Fact|date=December 2007}} Some sildenafil users have complained of seeing everything tinted blue ([[cyanopsia]]). <ref>{{cite web|url=http://www.visionweb.com/content/consumers/dev_consumerarticles.jsp?RID=85|title= Viagra and vision |date=n.d.|publisher= visionweb}}</ref>. Some complained of blurriness and loss of [[peripheral vision]]. In May of 2005, the [[United States|U.S.]] [[Food and Drug Administration]] found that sildenafil could lead to vision impairment<ref>{{cite web|url=http://www.fda.gov/cder/drug/InfoSheets/HCP/sildenafilHCP.htm|title=Alert for Healthcare Professionals: Sildenafil citrate (marketed as Viagra)|date=July 2005|publisher=United States Food and Drug Administration}}</ref> and a number of studies have linked sildenafil use with [[Anterior ischemic optic neuropathy|nonarteritic anterior ischemic optic neuropathy]].<ref>{{cite journal|author=Pomeranz HD and Bhavsar AR|title=Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases|journal=J Neuroophthalmol|year=2005|volume=25|issue=1|pages=9–13|pmid=15756125}}</ref><ref>{{cite journal|author=Egan R and Pomeranz H|title=Sildenafil (Viagra) associated anterior ischemic optic neuropathy|journal=Arch Ophthalmol|year=2000|volume=118|issue=2|pages=291–2|pmid=10676804}}</ref><ref>{{cite journal|author=Pomeranz HD, Smith KH, Hart WM, Egan RA|title=Sildenafil-associated nonarteritic anterior ischemic optic neuropathy|journal=Ophthalmology|year=2002|volume=109|issue=3|pages=584–7|pmid=11874765 | doi = 10.1016/S0161-6420(01)00976-9 <!--Retrieved from CrossRef by DOI bot-->}}</ref><ref>{{cite journal|author=Cunningham AV and Smith KH|title=Anterior ischemic optic neuropathy associated with viagra|journal=J Neuroophthalmol|year=2001|volume=21|issue=1|pages=22–5|pmid=11315976}}</ref><ref>{{cite journal|author=Boshier A, Pambakian N, Shakir SA|title=A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil|journal=Int J Clin Pharmacol Ther|year=2002|volume=40|issue=9|pages=422–3|pmid=12358159}}</ref><ref>{{cite journal|author=Akash R, Hrishikesh D, Amith P, Sabah S|title=Case report: association of combined nonarteritic anterior ischemic optic neuropathy (NAION) and obstruction of cilioretinal artery with overdose of Viagra|journal=J Ocul Pharmacol Ther|year=2005|volume=24|issue=4|pages=315–7|pmid=16117695|doi=10.1089/jop.2005.21.315}}</ref> In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil, requires a more prominent warning of the potential risk of [[Deafness|sudden hearing loss]] as the result of postmarketing reports of deafness associated with use of PDE5 inhibitors.<ref name="FDA PDE5">{{cite web | url= http://www.fda.gov/bbs/topics/NEWS/2007/NEW01730.html| title= FDA Announces Revisions to Labels for Cialis, Levitra and Viagra| author= | date= 2007-10-18| publisher= [[Food and Drug Administration]]| accessdate=2007-12-08 }}</ref> When used with an [[alpha blocker]], [[hypotension]] (low blood pressure) may occur, but this effect does not occur if they are taken at least four hours apart.<ref>{{cite journal|author=Kloner RA|title=Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions|journal=Am J Cardiol|year=2005|volume=96|issue=12B|pages=42M–46M|pmid=16387566 | doi = 10.1016/j.amjcard.2005.07.011 <!--Retrieved from CrossRef by DOI bot-->}}</ref> ==Other uses== ===Pulmonary hypertension=== As well as erectile dysfunction, sildenafil citrate is also effective in the [[rare disease]] [[pulmonary hypertension|pulmonary arterial hypertension]] (PAH). It relaxes the arterial wall, leading to decreased pulmonary arterial resistance and pressure. This in turn reduces the workload of the right [[ventricle (heart)|ventricle]] of the heart and improves symptoms of right-sided [[heart failure]]. Because PDE-5 is primarily distributed within the arterial wall smooth muscle of the lungs and penis, sildenafil acts selectively in both these areas without inducing vasodilation in other areas of the body. Pfizer submitted an additional registration for sildenafil to the FDA, and sildenafil was approved for this indication in June [[2005]]. The preparation is named Revatio, to avoid confusion with Viagra, and the 20 milligram tablets are white and round. Sildenafil joins [[bosentan]] and [[prostacyclin]]-based therapies for this condition.<ref>{{cite web | author = Pfizer, Inc. | year = June 6, 2005 | url = http://www.pfizer.com/pfizer/are/news_releases/2005pr/mn_2005_0606.jsp | title = FDA Approves Pfizer's Revatio as Treatment for Pulmonary Arterial Hypertension | work = 2005 News Releases | publisher = Pfizer | accessdate = December 27 | accessyear = 2005}}</ref> ===Raynaud's phenomenon=== In 2005, Dr. Roland Fries and colleagues reported that sildenafil cut the frequency of [[Raynaud's phenomenon]] attacks, reduced their duration by roughly one half, and more than quadrupled the mean capillary blood velocity. This was a double-blind, placebo-controlled crossover trial and the patients had both the primary and secondary forms and had all discontinued the more conventional treatments for this.<ref>{{cite journal | first = Roland | last = Fries | coauthors = Kaveh Shariat, Hubertus von Wilmowsky, and Michael Böhm | date = [[November 8]], [[2005]] | title = Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy | journal = Circulation | volume = 112 | issue = 19 | pages = 2980–5 | pmid = 16275885 | doi = 10.1161/CIRCULATIONAHA.104.523324 | url = http://circ.ahajournals.org/cgi/content/full/112/19/2980 | doi_brokendate = 2008-06-25}}</ref> ===Altitude sickness=== Sildenafil has been shown to be useful for the prevention and treatment of [[High altitude pulmonary edema]] associated with altitude sickness such as that suffered by mountain climbers.<ref>{{cite journal |author=Richalet JP, Gratadour P, Robach P, ''et al'' |title=Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension |journal=Am. J. Respir. Crit. Care Med. |volume=171 |issue=3 |pages=275–81 |year=2005 |pmid=15516532 |doi=10.1164/rccm.200406-804OC}}</ref><ref>{{cite journal |author=Perimenis P |title=Sildenafil for the treatment of altitude-induced hypoxaemia |journal=Expert Opin Pharmacother |volume=6 |issue=5 |pages=835–7 |year=2005 |pmid=15934909 |doi=10.1517/14656566.6.5.835}}</ref> While this effect has only recently been discovered, sildenafil is already becoming an accepted treatment for this condition, particularly in situations where the standard treatment of rapid descent has been delayed for some reason.<ref>{{cite journal |author=Fagenholz PJ, Gutman JA, Murray AF, Harris NS |title=Treatment of high altitude pulmonary edema at 4240 m in Nepal |journal=High Alt. Med. Biol. |volume=8 |issue=2 |pages=139–46 |year=2007 |pmid=17584008 |doi=10.1089/ham.2007.1055}}</ref> ===Duchenne/Becker Muscular Dystrophy=== Sildenafil has recently been used to enhance [[cGMP]] signaling, specifically downstream and independent of NO formation, in [[dystrophin]]-deficient mouse hearts. Chronic treatment improved contractile performance, myocardial metabolic status, and sarcolemmal integrity, highlighting its potential clinical avenue for the treatment of the dystrophin-related cardiomyopathies. <ref>{{cite journal |author=Khairallah M, Khairallah RJ, Young ME, ''et al'' |title=Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. |journal=Proc. Nat. Acad. Sci. U.S.A. |volume=105 |issue=19 |pages=7028–33 |year=2008 |pmid=18474859 |doi=10.1073/pnas.0710595105}}</ref> ===Use in sports=== Professional sports players have been using drugs such as Viagra thinking that the opening of their blood vessels will enrich their muscles, therefore enhancing their performance.<ref>{{cite web | coauthors = Teri Thompson, Christian Red, Michael O'Keefffe, and Nathaniel Vinton | title = Source: Roger Clemens, host of athletes pop Viagra to help onfield performance | publisher = New York Daily News | date = 2008-6-10 | url = http://www.nydailynews.com/sports/baseball/yankees/2008/06/09/2008-06-09_source_roger_clemens_host_of_athletes_po.html }}</ref> ==Non-medical use== ===Aphrodisiac=== Sildenafil is commonly and increasingly used as an [[aphrodisiac]], i.e. to increase [[sexual desire]]. However, there is no clinical evidence that it has aphrodisiac activity, because it does not have any direct effect on the brain, although increased ability to attain an erection may be interpreted as increased sexual arousal by users of these drugs. ===Recreational use=== Viagra's popularity with young adults has increased over the years.<ref>{{cite news|author=Peterson K|url=http://www.usatoday.com/news/health/2001-03-21-viagra-abuse.htm|title=Young men add Viagra to their drug arsenal|publisher=USAToday|date=[[2001-03-21]]}}</ref> It is sometimes used recreationally. Some users mix Viagra with [[methylenedioxymethamphetamine]] (MDMA, ecstasy) in an attempt to compensate for the side effect common to many amphetamines of erectile dysfunction, a combination known as "[[sextasy]]", "rockin' and rollin'", or 'trail mix'." ===Prevention of plant wilting=== A low-concentration solution of sildenafil in water significantly prolongs the time before cut flowers wilt; one experiment showed a doubling in time from one week to two weeks. The mechanism of action is similar to that in humans: nitric oxide leads to the production of cGMP whose degradation by PDE5 is inhibited by sildenafil.<ref>{{cite journal|author=Siegel-Itzkovich J|url=http://www.studentbmj.com/issues/99/09/news/313.php|title=Viagra makes flowers stand up straight|journal=Student BMJ|year=1999|issue=9}}</ref> === Jet lag research === The 2007 [[Ig Nobel Prize]] in Aviation went to Patricia V. Agostino, Santiago A. Plano and Diego A. Golombek of Universidad Nacional de Quilmes, Argentina, for their discovery that Viagra aids [[jet lag]] recovery in hamsters.<ref>[http://www.improbable.com/ig/ig-pastwinners.html#ig2007]</ref> Their research was published in the [[Proceedings of the National Academy of Sciences]].<ref>{{cite journal |author=Agostino PV, Plano SA, Golombek DA |title=Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=23 |pages=9834–9 |year=2007 |pmid=17519328 |doi=10.1073/pnas.0703388104}}</ref> ==Chemical synthesis== The preparation steps for synthesis of Viagra (sildenafil citrate) are as follows: # [[Methylation]] of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate. # [[Hydrolysis]] with aqueous NaOH to free acid. # [[Nitration]] with oleum/fuming nitric acid. # Carboxamide formation with refluxing thionyl chloride/NH4OH. # [[Redox|Reduction]] of nitro group to amino. # [[Acylation]] with 2-ethoxybenzoyl chloride. # Cyclization. # [[Sulfonation]] to the chlorosulfonyl derivative. # [[Condensation]] with 1-methylpiperazine.<ref>{{cite journal|journal = Org Process Res Dev| volume = 2005 |issue =1 |pages = 88–97 |doi = 10.1021/op040019c S1083-6160(04)00019-2| title = Synthesis of Commercial Phosphodiesterase(V) Inhibitors | author = Dunn PJ | year = 2005}}</ref> ==See also== * [[Tadalafil]] (Cialis) * [[Vardenafil]] (Levitra) * [[Yohimbine]] ==References== {{refimprove|date=March 2008}} {{reflist}} ==External links== {{commonscat|Viagra}} * [http://www.viagra.com/ Home page for Viagra] * [http://www.revatio.com Home page for Revatio] * [http://www.pfizer.com/ Pfizer Pharmaceutical (Company website)] - manufacturer of Viagra; [http://www.pfizer.com/files/products/uspi_viagra.pdf prescribing information for Viagra] and [http://www.pfizer.com/files/products/uspi_revatio.pdf prescribing information for Revatio] available in PDF format. * [http://www.fda.gov/cder/consumerinfo/viagra/ FDA Web Site for Viagra Consumer Information] *[http://www.fda.gov/cder/foi/label/2005/020895s021lbl.pdf FDA current Viagra label (a form of clinical information and report)] *[http://www.nlm.nih.gov/medlineplus/print/druginfo/uspdi/203533.html MedlinePLUS drug Information] - Side Effects of sildenafil * [http://science.howstuffworks.com/viagra.htm/printable How Viagra Works] - [[Howstuffworks]] article * [http://www.myscienceproject.org/viagra-flowers.html Does Viagra Keep Flowers From Wilting?] {{Urologicals}} {{PAH rx}} {{Phosphodiesterase inhibitors}} [[Category:PDE5 inhibitors]] [[Category:Citrates]] {{Link FA|pl}} <!-- The below are interlanguage links. --> [[ar:سيلدينافيل]] [[ca:Sildenafil]] [[cs:Sildenafil]] [[da:Viagra]] [[de:Sildenafil]] [[es:Sildenafil]] [[fr:Sildénafil]] [[id:Sildenafil]] [[it:Sildenafil]] [[he:ויאגרה]] [[hu:Sildenafil]] [[nl:Sildenafil]] [[ja:クエン酸シルデナフィル]] [[no:Sildenafil]] [[pl:Sildenafil]] [[pt:Sildenafila]] [[ru:Силденафил]] [[sq:Sildenafil]] [[simple:Sildenafil]] [[sl:Sildenafil]] [[fi:Sildenafiili]] [[sv:Sildenafil]] [[th:ไวอะกร้า]] [[vi:Viagra]] [[tr:Sildenafil]] [[uk:Силденафіл]] [[bat-smg:Sildenafil]] [[zh:西地那非]]