There are also mouth spray preparations of sildenafil for faster onset of action. Chemical synthesis
The preparation steps for synthesis of sildenafil are:
Methylation of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate
Hydrolysis with aqueous sodium hydroxide (NaOH) to free acid
Nitration with oleum/fuming nitric acid
Carboxamide formation with refluxing thionyl chloride/NH4OH
Reduction of nitro group to amino group
Acylation with 2-ethoxybenzoyl chloride
Cyclization
Sulfonation to the chlorosulfonyl derivative
Condensation with 1-methylpiperazine. History
Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizers 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). The first clinical trials were conducted in Morriston Hospital in Swansea. 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. Pfizer therefore decided to market it for erectile dysfunction, rather than for angina; this decision became an often-cited example of drug repositioning. 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. It soon became a great success: annual sales of Viagra peaked in 2008 at US$1.934 billion.
Contraindications
Contraindications include:
Concomitant use of nitric oxide donors, organic nitrites and nitrates, 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 sildenafilSildenafil should not be used if sexual activity is inadvisable due to underlying cardiovascular risk factors. Nonmedical use
Recreational use
Sildenafils popularity with young adults has increased over the years. Sildenafils trade name, Viagra, is widely recognized in popular culture, and the drugs association with treating erectile dysfunction has led to its recreational use. The reasons behind such use include the belief that the drug increases libido, improves sexual performance, or permanently increases penis size. 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. This study also noted a significant placebo effect in the control group.Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high among users of illegal drugs. Sildenafil is sometimes used to counteract the effects of other substances, often illicit. 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" or "trail mix". Mixing it with amyl nitrite, another vasodilator, is particularly dangerous and potentially fatal.