Sildenafil

Sildenafil (Viagra) is used to treat erectile dysfunction (impotence; inability to get or keep an erection) in men. Sildenafil (Liqrev, Revatio) is used to improve the ability to exercise in adults (Liqrev, Revatio) and children 1 year of age and older (Revatio) with pulmonary arterial hypertension (PAH; high blood pressure in the vessels carrying blood to the lungs, causing shortness of breath, dizziness, and tiredness).

Sildenafil is in a class of medications called phosphodiesterase (PDE) inhibitors. Sildenafil treats erectile dysfunction by increasing blood flow to the penis during sexual stimulation. This increased blood flow can cause an erection. Sildenafil treats PAH by relaxing the blood vessels in the lungs to allow blood to flow easily.

Key Facts About Sildenafil:

• Mechanism: It inhibits an enzyme called PDE5, enhancing nitric oxide–mediated vasodilation.
• Onset: Typically works within 30–60 minutes.
• Duration: Effects can last 4–6 hours.
• Side effects: Common ones include headache, flushing, nasal congestion, dizziness, and upset stomach. Rarely, it can cause vision changes or priapism (a prolonged erection).

If you are taking sildenafil to treat erectile dysfunction, you should know that it does not cure erectile dysfunction or increase sexual desire. Sildenafil does not prevent pregnancy or the spread of sexually transmitted diseases such as human immunodeficiency virus (HIV).

Sildenafil, sold under the brand name Viagra among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension.^[5][9] It is also sometimes used off-label for the treatment of certain symptoms in secondary Raynaud’s phenomenon.^[10] It is unclear if it is effective for treating sexual dysfunction in females.^[9] It can be taken orally (swallowed by mouth), intravenously (injection into a vein), or through the sublingual route (dissolved under the tongue).^[9][11] Onset when taken orally is typically within twenty minutes and lasts for about two hours.^[9]

Sildenafil is a medication primarily used to treat erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). It’s best known under the brand name Viagra when used for ED. It works by relaxing blood vessels and increasing blood flow to particular areas of the body, such as the penis.

Key Facts About Sildenafil:

• Mechanism: It inhibits an enzyme called PDE5, enhancing nitric oxide–mediated vasodilation.
• Onset: Typically works within 30–60 minutes.
• Duration: Effects can last 4–6 hours.
• Side effects: Common ones include headache, flushing, nasal congestion, dizziness, and upset stomach. Rarely, it can cause vision changes or priapism (a prolonged erection).

How to Buy Sildenafil Online

1. Prescription Requirement:

• • In many countries, including the U.S., UK, and most of Europe, sildenafil requires a prescription.
  • Some online platforms offer telehealth consultations to get a prescription.

1. Choose a Reputable Source:
   • Use licensed pharmacies or platforms like:

• • • RexMD, Hims, Ro (U.S.)
    • Superdrug Online Doctor, LloydsPharmacy Online (UK)
    • Or your local online pharmacy.

1. • Avoid unverified sites—counterfeit drugs are a serious risk.
2. Steps to Buy:

• • Complete an online health questionnaire or consult with a licensed provider.
  • If approved, you’ll get a prescription.
  • Sildenafil will be shipped discreetly to your address.

1. Generic vs Brand:
   • Generic sildenafil is cheaper than brand-name Viagra and equally effective.
2. Watch for Red Flags:
   • Avoid websites that:

• • • Don’t require a prescription.
    • Offer extremely low prices.
    • Lack contact details or regulatory credentials.

Common side effects include headaches, heartburn, and flushed skin.^[9] Caution is advised in those with cardiovascular disease.^[9] Rare but serious side effects include vision problems, hearing loss, and prolonged erection (priapism) that can lead to damage to the penis.^[9] Sildenafil should not be taken by people on nitric oxide donors such as nitroglycerin, as this may result in a serious drop in blood pressure.^[9]

Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis.^[9] It requires sexual arousal to work, and does not by itself cause or increase sexual arousal.^[9] It also results in dilation of the blood vessels in the lungs.^[9]

Pfizer originally discovered the medication in 1989 while looking for a treatment for angina.[12] It was approved for medical use in the United States and in the European Union in 1998.[6][9][12][13] In 2022, it was the 157th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[14][15] It is available as a generic medication.[16][17] In the United Kingdom, it is available over-the-counter (OTC).[18]

The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete sexual intercourse). Its use is now one of the standard treatments for erectile dysfunction, including for males with diabetes mellitus.[19]

Tentative evidence suggests that sildenafil may help males who experience antidepressant-induced erectile dysfunction.[20]

While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of death or serious side effects.[21]

Sildenafil and other PDE5 inhibitors are used off-label to alleviate vasospasm and treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud’s phenomenon;[10][22] these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes.[10] As of 2016, their role more generally in Raynaud’s was not clear.[22]

Sildenafil has shown some potential for improving exercise performance at high altitudes. However, its overall efficacy is not clear.[23]

Sildenafil has been studied for high-altitude pulmonary edema (HAPE), but its use is currently not recommended for that indication.[24]

In clinical trials, the most common adverse effects of sildenafil use included headache, flushing, indigestion, nasal congestion, and impaired vision, including photophobia and blurred vision.[5] Some sildenafil users have complained of seeing everything tinted blue (cyanopsia).[25] This cyanopsia can be explained because sildenafil, while selective for PDE5, does have some affinity for PDE6, which is the phosphodiesterase found in the retina. Patients thus taking the drug may experience colorvision abnormalities. Some complained of blurriness and loss of peripheral vision. In July 2005, the US Food and Drug Administration (FDA) updated labeling for tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra) to reflect a small number of post-marketing reports of sudden vision loss, while acknowledging that “…it is not possible to determine whether these oral medicines for erectile dysfunction were the cause of the loss of eyesight or whether the problem is related to other factors such as high blood pressure or diabetes, or to a combination of these problems.”[26] A careful review of pooled data from clinical trials containing well documented information about the dose and duration of exposure to the drug for a large number of patients, yields no evidence for an increased risk of non-arteritic anterior ischemic optic neuropathy or other adverse ocular events associated with PDE5 inhibitor use.[27]

Rare but serious adverse effects found through postmarketing surveillance include prolonged erections, severe low blood pressure, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss.[5] In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil, required a more prominent warning of the potential risk of sudden hearing loss.[28]

Care should be exercised by people who are also taking protease inhibitors for the treatment of HIV infection. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying the plasma levels of sildenafil, increasing the incidence and severity of side effects. Those using protease inhibitors are recommended to limit their use of sildenafil to no more than one 25 mg dose every 48 hours.[5] Other drugs that interfere with the metabolism of sildenafil include erythromycin and cimetidine, both of which can also lead to prolonged plasma half-life levels.[29]

The use of sildenafil and an α1 blocker (typically prescribed for hypertension or for urologic conditions, such as benign prostatic hypertrophy) at the same time may lead to low blood pressure, but this effect does not occur if they are taken at least 4 hours apart.[30]

Contraindications include:[5]

• Concomitant use of nitric oxide donors, organic nitrites and nitrates,[31] such as:
  • nitroglycerin
  • isosorbide mononitrate
  • isosorbide dinitrate
  • sodium nitroprusside
  • alkyl nitrites (commonly known as “poppers”)
• Concomitant use of soluble guanylyl cyclase stimulators, such as riociguat
• Known hypersensitivity to sildenafil

Sildenafil should not be used if sexual activity is inadvisable due to underlying cardiovascular risk factors.[32]

Sildenafil’s popularity with young adults has increased over the years.[33] Sildenafil’s brand name, Viagra, is widely recognized in popular culture, and the drug’s association with treating erectile dysfunction has led to its recreational use.[34] The reasons behind such use include the belief that the drug increases libido, improves sexual performance,[34] or permanently increases penis size.[35] Studies on the effects of sildenafil when used recreationally are limited, but suggest it has little effect when used by those who do not have erectile dysfunction. In one study, a 25 mg dose was shown to cause no significant change in erectile quality, but did reduce the postejaculatory refractory time.[36] This study also noted a significant placebo effect in the control group.[36]

Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high among users of illegal drugs.[37] Sildenafil is sometimes used to counteract the effects of other substances, often illicit.[34] Some users mix it with methylenedioxymethamphetamine (MDMA, ecstasy), other stimulants, or opiates in an attempt to compensate for the common side effect of erectile dysfunction, a combination known as “sextasy”, “rockin’ and rollin'”, “hammerheading”, or “trail mix”.[34] Mixing it with amyl nitrite, another vasodilator, is particularly dangerous and potentially fatal.[34]

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 sildenafil helps treat jet lag recovery in hamsters.[38][39]

Professional athletes have been documented using sildenafil, believing the opening of their blood vessels will enrich their muscles. In turn, they believe it will enhance their performances.[40][41]

Acetildenafil and other synthetic structural analogs of sildenafil which are PDE5 inhibitors have been found as adulterants in a number of “herbal” aphrodisiac products sold over-the-counter.[42] These analogs have not undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have unknown side-effect profiles.[43] Some attempts have been made to ban these drugs, but progress has been slow so far, as, even in those jurisdictions that have laws targeting designer drugs, the laws are drafted to ban analogs of illegal drugs of abuse, rather than analogs of prescription medicines. However, at least one court case has resulted in a product being taken off the market.[44]

The US Food and Drug Administration (FDA) has banned numerous products claiming to be Eurycoma longifolia that, in fact, contain only analogs of sildenafil.[45][46][47] Sellers of such fake herbals typically respond by just changing the names of their products.

Sildenafil and/or N-desmethylsildenafil, its major active metabolite, may be quantified in plasma, serum, or whole blood to assess pharmacokinetic status in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdose.[48]

Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum. Nitric oxide (NO) in the corpus cavernosum of the penis binds to guanylate cyclase receptors, which results in increased levels of cGMP, leading to smooth muscle relaxation (vasodilation) of the intimal cushions of the helicine arteries. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection.[50] Robert F. Furchgott, Ferid Murad, and Louis Ignarro won the Nobel Prize in Physiology or Medicine in 1998 for their independent study of the metabolic pathway of nitric oxide in smooth muscle vasodilation.

The molecular mechanism of smooth muscle relaxation involves the enzyme CGMP-dependent protein kinase, also known as PKG. This kinase is activated by cGMP and it phosphorylates multiple targets in the smooth muscle cells, namely myosin light chain phosphatase, RhoA, IP3 receptor, phospholipase C, and others.[51] Overall, this results in a decrease in intracellular calcium and desensitizing proteins to the effects of calcium, engendering smooth muscle relaxation.[51]

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. 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 increased penile response to sexual stimulation.[50][52] 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 broken down in the liver by hepatic metabolism using cytochrome p450 enzymes, mainly CYP450 3A4 (major route), but also by CYP2C9 (minor route) hepatic isoenzymes. The major product of metabolisation by these enzymes is N-desmethylated sildenafil, which is metabolised further. This metabolite also has an affinity for the PDE receptors, about 40% of that of sildenafil. Thus, the metabolite is responsible for about 20% of sildenafil’s action. Sildenafil is excreted as metabolites predominantly in the feces (about 80% of administered oral dose) and to a lesser extent in the urine (around 13% of the administered oral dose). If taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.[53]

• When taken orally, sildenafil for erectile dysfunction results in an average time to onset of erections of 27 minutes (ranging from 12 to 70 minutes).[54]
• Sublingual use of sildenafil for erectile dysfunction results in an average onset of action of 15 minutes and lasting for an average of 40 minutes.[11]

The preparation steps for synthesis of sildenafil are:[55]

1. Methylation of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate
2. Hydrolysis with aqueous sodium hydroxide (NaOH) to free acid
3. Nitration with oleum/fuming nitric acid
4. Carboxamide formation with refluxing thionyl chloride/NH4OH
5. Reduction of nitro group to amino group
6. Acylation with 2-ethoxybenzoyl chloride
7. Cyclization
8. Sulfonation to the chlorosulfonyl derivative
9. Condensation with 1-methylpiperazine.

Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists led by Simon Campbell[56] 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 heart disease).[57] The first clinical trials were conducted in Morriston Hospital in Swansea.[58] Phase I clinical trials under the direction of Ian Osterloh suggested the drug had little effect on angina, but it could induce marked penile erections.[59][60] Pfizer therefore decided to market it for erectile dysfunction, rather than for angina; this decision became an often-cited example of drug repositioning.[61][62] The drug was patented in 1996, approved for use in erectile dysfunction by the FDA on 27 March 1998, becoming the first oral treatment approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year.[63] It soon became a great success: annual sales of Viagra peaked in 2008 at US$1.934 billion.[64]

Reference

• “Sildenafil Use During Pregnancy”. Drugs.com. 7 October 2019. Archived from the original on 12 October 2020. Retrieved 6 October 2020.
• “MHRA reclassifies Viagra Connect tablets to a Pharmacy medicine”.
• “Viagra can be sold over the counter”. BBC News. 28 November 2017.
• “Viagra to be available without prescription in UK”. CNN. 28 November 2017.
• “Viagra- sildenafil citrate tablet, film coated”. DailyMed. Archived from the original on 13 August 2020. Retrieved 6 October 2020.
• “Viagra EPAR”. European Medicines Agency. 17 September 2018. Archived from the original on 11 October 2020. Retrieved 6 October 2020.
• “Revatio EPAR”. European Medicines Agency. 17 September 2018. Archived from the original on 11 November 2020. Retrieved 6 October 2020.
• Nichols DJ, Muirhead GJ, Harness JA (6 March 2002). “Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality”. British Journal of Clinical Pharmacology. 53 (Suppl 1): 5S – 12S. doi:10.1046/j.0306-5251.2001.00027.x. PMC 1874258. PMID 11879254.
• “Sildenafil Citrate”. The American Society of Health-System Pharmacists. Archived from the original on 23 April 2020. Retrieved 1 December 2014.
• Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL (October 2013). “Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomised trials”. Annals of the Rheumatic Diseases. 72 (10): 1696–9. doi:10.1136/annrheumdis-2012-202836. PMID 23426043. S2CID 33666968. PDE-5 inhibitors appear to have significant but moderate efficacy in secondary [Raynaud’s phenomenon].
• Deveci S, Peşkircioğlu L, Aygün C, Tekin MI, Dirim A, Ozkardeş H (November 2004). “Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with less dose”. International Journal of Urology. 11 (11): 989–92. doi:10.1111/j.1442-2042.2004.00933.x. PMID 15509203. S2CID 28302024.
• Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ (January 2019). “The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction”. Sexual Medicine Reviews. 7 (1): 115–128. doi:10.1016/j.sxmr.2018.06.005. PMID 30301707. S2CID 52945888.
• “Drug Approval Package: Viagra (sildenafil citrate) NDA #020895”. U.S. Food and Drug Administration (FDA). 27 March 1998. Archived from the original on 31 March 2021. Retrieved 15 February 2021.
• “The Top 300 of 2022”. ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
• “Sildenafil Drug Usage Statistics, United States, 2013 – 2022”. ClinCalc. Retrieved 30 August 2024.
• Gordon S (11 December 2017). “Generic Viagra: Two versions of sildenafil hit the market today”. CBS News. Archived from the original on 25 November 2018. Retrieved 24 November 2018.
• “Competitive Generic Therapy Approvals”. U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 12 February 2022. Retrieved 6 March 2023.
• LaMattina J. “With Viagra Now Available Over-The-Counter In The U.K., Will The U.S. Follow Suit?”. Forbes. Archived from the original on 25 November 2018. Retrieved 24 November 2018.
• Vardi M, Nini A (January 2007). “Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus”. The Cochrane Database of Systematic Reviews. 2009 (1): CD002187. doi:10.1002/14651858.CD002187.pub3. PMC 6718223. PMID 17253475.
• Taylor MJ, Rudkin L, Bullemor-Day P, Lubin J, Chukwujekwu C, Hawton K (May 2013). “Strategies for managing sexual dysfunction induced by antidepressant medication”. The Cochrane Database of Systematic Reviews (5): CD003382. doi:10.1002/14651858.CD003382.pub3. PMID 23728643. Archived from the original on 10 October 2020. Retrieved 30 November 2019.
• Wang RC, Jiang FM, Zheng QL, Li CT, Peng XY, He CY, et al. (March 2014). “Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review”. Respiratory Medicine. 108 (3): 531–7. doi:10.1016/j.rmed.2014.01.003. PMID 24462476. Archived from the original on 29 August 2021. Retrieved 5 November 2016.
• Linnemann B, Erbe M (2016). “Raynaud’s phenomenon and digital ischaemia–pharmacologic approach and alternative treatment options”. VASA. Zeitschrift für Gefässkrankheiten. 45 (3): 201–12. doi:10.1024/0301-1526/a000526. PMID 27129065. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve [Raynaud’s phenomenon] symptoms and ulcer healing
• Dang ZC, Yang Z, Liu S, Du GM, Jin L, Zhao ZZ (February 2024). “Efficacy of Sildenafil on healthy humans in high‑altitude hypoxia at rest and during exercise: A meta‑analysis”. Experimental and Therapeutic Medicine. 27 (2): 88. doi:10.3892/etm.2024.12376. PMC 10809317. PMID 38274336.
• Nieto Estrada VH, Molano Franco D, Medina RD, Gonzalez Garay AG, Martí-Carvajal AJ, Arevalo-Rodriguez I (June 2017). “Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs”. The Cochrane Database of Systematic Reviews. 6 (12): CD009761. doi:10.1002/14651858.CD009761.pub2. PMC 6481751. PMID 28653390.
• “Viagra and Vision”. VisionWeb. 29 October 2001. Archived from the original on 10 June 2017. Retrieved 5 November 2016.
• “FDA Updates Labeling for Viagra, Cialis and Levitra for Rare Post-Marketing Reports of Eye Problems” (Press release). U.S. Food and Drug Administration (FDA). 8 July 2005. Archived from the original on 22 October 2016. Retrieved 5 November 2016.
• Laties AM (January 2009). “Vision disorders and phosphodiesterase type 5 inhibitors: a review of the evidence to date”. Drug Safety. 32 (1): 1–18. doi:10.2165/00002018-200932010-00001. PMID 19132801. S2CID 207296076.
• “FDA Announces Revisions to Labels for Cialis, Levitra and Viagra”. U.S. Food and Drug Administration (FDA). 18 October 2007. Archived from the original on 22 October 2016. Retrieved 5 November 2016.
• Schwartz BG, Kloner RA (July 2010). “Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension”. Circulation. 122 (1): 88–95. doi:10.1161/CIRCULATIONAHA.110.944603. PMID 20606131. S2CID 13207143.
• Kloner RA (December 2005). “Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions”. The American Journal of Cardiology. 96 (12B): 42M – 46M. doi:10.1016/j.amjcard.2005.07.011. PMID 16387566.
• Cheitlin MD, Hutter AM, Brindis RG, Ganz P, Kaul S, Russell RO, et al. (January 1999). “ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association”. Journal of the American College of Cardiology. 33 (1): 273–82. doi:10.1016/S0735-1097(98)00656-1. PMID 9935041.
• “Viagra (Sildenafil Citrate): Side Effects, Interactions, Warning, Dosage & Uses”. RxList. Archived from the original on 12 July 2018. Retrieved 11 July 2018.
• Peterson K (21 March 2001). “Young men add Viagra to their drug arsenal”. USA Today. Archived from the original on 4 September 2014. Retrieved 27 December 2013.
• Smith KM, Romanelli F (2005). “Recreational use and misuse of phosphodiesterase 5 inhibitors”. Journal of the American Pharmacists Association. 45 (1): 63–72, quiz 73–5. doi:10.1331/1544345052843165. PMID 15730119.
• “Sildenafil Will Not Affect Libido – Fact!”. Archived from the original on 21 August 2016. Retrieved 15 July 2016.
• Mondaini N, Ponchietti R, Muir GH, Montorsi F, Di Loro F, Lombardi G, et al. (June 2003). “Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time”. International Journal of Impotence Research. 15 (3): 225–8. doi:10.1038/sj.ijir.3901005. PMID 12904810. S2CID 22508049.
• McCambridge J, Mitcheson L, Hunt N, Winstock A (March 2006). “The rise of Viagra among British illicit drug users: 5-year survey data”. Drug and Alcohol Review. 25 (2): 111–3. doi:10.1080/09595230500537167. PMID 16627299. S2CID 40250895.
  – Eloi-Stiven ML, Channaveeraiah N, Christos PJ, Finkel M, Reddy R (November 2007). “Does marijuana use play a role in the recreational use of sildenafil?”. The Journal of Family Practice. 56 (11): E1-4. PMID 17976333.
• “The 2007 Ig Nobel Prize Winners”. Improbable Research. 4 October 2007. Archived from the original on 26 January 2013. Retrieved 10 February 2009.
• Agostino PV, Plano SA, Golombek DA (June 2007). “Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules”. Proceedings of the National Academy of Sciences of the United States of America. 104 (23): 9834–9. Bibcode:2007PNAS..104.9834A. doi:10.1073/pnas.0703388104. PMC 1887561. PMID 17519328.
• Thompson T, Red C, O’Keefffe M, Vinton N (10 June 2008). “Source: Roger Clemens, host of athletes pop Viagra to help onfield performance”. Daily News. Archived from the original on 14 August 2020. Retrieved 10 February 2009.
• Busbee J (28 November 2012). “Bears’ Brandon Marshall says some NFL players use Viagra … ON THE FIELD”. Yahoo! Sports. Archived from the original on 5 March 2016. Retrieved 28 November 2012.
• Venhuis BJ, de Kaste D (October 2012). “Towards a decade of detecting new analogues of sildenafil, tadalafil and vardenafil in food supplements: a history, analytical aspects and health risks”. Journal of Pharmaceutical and Biomedical Analysis. 69: 196–208. doi:10.1016/j.jpba.2012.02.014. PMID 22464558.
• Oh SS, Zou P, Low MY, Koh HL (November 2006). “Detection of sildenafil analogues in herbal products for erectile dysfunction”. Journal of Toxicology and Environmental Health. Part A. 69 (21): 1951–8. Bibcode:2006JTEHA..69.1951S. doi:10.1080/15287390600751355. PMID 16982533. S2CID 40831895.
• Venhuis BJ, Blok-Tip L, de Kaste D (May 2008). “Designer drugs in herbal aphrodisiacs”. Forensic Science International. 177 (2–3): e25-7. doi:10.1016/j.forsciint.2007.11.007. PMID 18178354.
• “FDA letter to Libidus distributor”. U.S. Food and Drug Administration (FDA). 11 July 2006. Archived from the original on 4 March 2016.
• “FDA Warns Consumers About Dangerous Ingredients in “Dietary Supplements” Promoted for Sexual Enhancement”. U.S. Food and Drug Administration (FDA). 12 July 2006. Archived from the original on 18 January 2017.
• “Hidden Risks of Erectile Dysfunction ‘Treatments’ Sold Online”. U.S. Food and Drug Administration (FDA). 21 February 2009. Archived from the original on 23 April 2019. Retrieved 8 December 2020.
• R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 1552–53. “Sildenafil” (PDF). Biomedical Publications. Archived from the original (PDF) on 10 September 2011. Retrieved 1 July 2011.
• Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, et al. (September 2003). “Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules”. Nature. 425 (6953): 98–102. Bibcode:2003Natur.425…98S. doi:10.1038/nature01914. PMID 12955149. S2CID 4404590.
• Webb DJ, Freestone S, Allen MJ, Muirhead GJ (March 1999). “Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist”. The American Journal of Cardiology. 83 (5A): 21C – 28C. doi:10.1016/S0002-9149(99)00044-2. PMID 10078539.
• Francis SH, Busch JL, Corbin JD, Sibley D (September 2010). “cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action”. Pharmacological Reviews. 62 (3): 525–63. doi:10.1124/pr.110.002907. PMC 2964902. PMID 20716671.
• Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA (May 1998). “Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group”. The New England Journal of Medicine. 338 (20): 1397–1404. doi:10.1056/NEJM199805143382001. PMID 9580646.
• “Viagra Clinical Pharmacology”. RxList.com. 2008. Archived from the original on 14 January 2012. Retrieved 20 August 2008.