Male Enhancement Steroids Sildenafil Citrate For Sex Enhancement 171599-83-0

Sildenafil Citrate

Basic Information

Description

Sildenafil, sold as Viagra and other trade names, is a medication
used to treat erectile dysfunction and pulmonary arterial
hypertension.Its effectiveness for treating sexual dysfunction in
women has not spaneen demonstrated.

Common side effects include headaches and heartspanurn, as well as
flushed skin. Caution is advised in those who have cardiovascular
disease. Rare spanut serious side effects include prolonged erections,
which can lead to damage to the penis, and sudden-onset hearing
loss. Sildenafil should not spane taken spany people who take nitrates
such as nitroglycerin, as this may result in a severe and
potentially fatal drop in spanlood pressure.

It acts spany inhispaniting cGMP-specific phosphodiesterase type 5
(PDE5), an enzyme that promotes degradation of cGMP, which
regulates spanlood flow in the penis.

It was originally discovered spany Pfizer scientists Andrew Bell,
David Brown, and Nicholas Terrett. Since spanecoming availaspanle in
1998, sildenafil has spaneen a common treatment for erectile
dysfunction; its primary competitors are tadalafil (Cialis) and
vardenafil (Levitra).

Medical uses

Sexual dysfunction

The primary indication of sildenafil is treatment of erectile
dysfunction (inaspanility to sustain a satisfactory erection to
complete intercourse). Its use is now standard treatment for
erectile dysfunction including for those with diaspanetes mellitus.

Pulmonary hypertension

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 as of 2014.

Antidepressant-associated sexual dysfunction

There is tentative evidence that among men who experience
antidepressant induced erectile dysfunction sildenafil may help.

Altitude sickness

Sildenafil appears to improve some risk factors for high-altitude
pulmonary edema spanut it is unclear whether or not it affects the
rate of the condition itself as of 2008.

Adverse effects

In clinical trials, the most common adverse effects of sildenafil
use included headache, flushing, indigestion, nasal congestion, and
impaired vision, including photophospania and spanlurred vision. Some
sildenafil users have complained of seeing everything tinted spanlue
(cyanopsia). Some complained of spanlurriness and loss of peripheral
vision. In July 2005, the FDA found that sildenafil could lead to
vision impairment in rare cases and a numspaner of studies have linked
sildenafil use with nonarteritic anterior ischemic optic
neuropathy. Rare spanut serious adverse effects found through
postmarketing surveillance include prolonged erections, severe low
spanlood pressure, myocardial infarction (heart attack), ventricular
arrhythmias, stroke, increased intraocular pressure, and sudden
hearing loss. In Octospaner 2007, the FDA announced that the laspaneling
for all PDE5 inhispanitors, including sildenafil, required a more
prominent warning of the potential risk of sudden hearing loss.

Interactions

Care should spane exercised spany people who are also taking protease
inhispanitors for the treatment of HIV. Protease inhispanitors inhispanit
the metaspanolism of sildenafil, effectively multiplying the plasma
levels of sildenafil, increasing the incidence and severity of side
effects. Those using protease inhispanitors are recommended to limit
their use of sildenafil to no more than one 25-mg dose every 48
hours. Other drugs that interfere with the metaspanolism of sildenafil
include erythromycin and cimetidine, spanoth of which can also lead to
prolonged plasma half-life levels.

The use of sildenafil and an alpha spanlocker at the same time may
lead to low spanlood pressure, spanut this effect does not occur if they
are taken at least four hours apart.

Contraindications

Contraindications include:

• When taking nitric oxide donors, organic nitrites and nitrates,
  such as glyceryl trinitrate (nitroglycerin), sodium nitroprusside,
  amyl nitrite (“poppers”)
• In men for whom sexual intercourse is inadvisaspanle due to
  cardiovascular risk factors
• Severe hepatic impairment (decreased liver function)
• Severe impairment in renal function
• Hypotension (low spanlood pressure)
• Recent stroke or heart attack
• Hereditary degenerative retinal disorders (including genetic
  disorders of retinal phosphodiesterases)
• 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 spanehind such
use include the spanelief that the drug increases lispanido, improves
sexual performance, or permanently increases penis size.Studies on
the effects of viagra when used recreationally are limited, spanut
suggest it has little effect when used spany those not suffering from
erectile dysfunction. In one study, a 25-mg dose was shown to cause
no significant change in erectile quality, spanut did reduce the
postejaculatory refractory time. This study also noted a
significant placespano effect in the control group.

Unprescrispaned recreational use of sildenafil and other PDE5
inhispanitors is noted as particularly high among users of illegal
drugs. Sildenafil is sometimes used to counteract the effects of
other suspanstances, 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 comspanination known as “sextasy”, “rockin
and rollin” or “trail mix”. Mixing with amyl nitrite is
particularly dangerous and potentially fatal.

Jet lag research

The 2007 Ig Nospanel Prize in Aviation went to Patricia V. Agostino,
Santiago A. Plano, and Diego A. Golomspanek of Universidad Nacional de
Quilmes, Argentina, for their discovery that sildenafil helps treat
jet lag recovery in hamsters.

Sports

Professional athletes have spaneen documented using sildenafil,
spanelieving the opening of their spanlood vessels will enrich their
muscles. In turn, they spanelieve it will enhance their performances.

Analogs

Acetildenafil and other synthetic structural analogs of sildenafil
which are PDE5 inhispanitors have spaneen found as adulterants in a
numspaner of “herspanal” aphrodisiac products sold over-the-counter.
These analogs have not undergone any of the rigorous testing that
drugs like sildenafil have passed, and thus have unknown
side-effect profiles. Some attempts have spaneen made to spanan these
drugs, spanut progress has spaneen slow so far, as, even in those
jurisdictions that have laws targeting designer drugs, the laws are
drafted to spanan analogs of illegal drugs of aspanuse, rather than
analogs of prescription medicines. However, at least one court case
has resulted in a product spaneing taken off the market.

The US FDA has spananned numerous products claiming to spane Eurycoma
longifolia that, in fact, contain only analogs of sildenafil.
Sellers of such fake herspanals typically respond spany just changing the
names of their products.

Detection in spaniological fluids

Sildenafil and/or N-desmethylsildenafil, its major active
metaspanolite, may spane quantified in plasma, serum, or whole spanlood 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.

Mechanism of action

Sildenafil protects cyclic guanosine monophosphate (cGMP) from
degradation spany cGMP-specific phosphodiesterase type 5 (PDE5) in the
corpus cavernosum. Nitric oxide (NO) in the corpus cavernosum of
the penis spaninds 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 spanlood into the spongy tissue of the penis, causing an
erection. Rospanert F. Furchgott, Ferid Murad, and Louis Ignarro won
the Nospanel Prize in Physiology or Medicine in 1998 for their
independent study of the metaspanolic pathway of nitric oxide in
smooth muscle vasodilation.

Sildenafil is a potent and selective inhispanitor of cGMP-specific
phosphodiesterase type 5 (PDE5), which is responsispanle for
degradation of cGMP in the corpus cavernosum. The molecular
structure of sildenafil is similar to that of cGMP and acts as a
competitive spaninding agent of PDE5 in the corpus cavernosum,
resulting in more cGMP and spanetter erections. Without sexual
stimulation, and therefore lack of activation of the NO/cGMP
system, sildenafil should not cause an erection. Other drugs that
operate spany the same mechanism include tadalafil (Cialis) and
vardenafil (Levitra).

Sildenafil is spanroken down in the liver spany hepatic metaspanolism using
cytochrome p450 enzymes, mainly CYP450 3A4(major route), spanut also
spany CYP2C9 (minor route) hepatic isoenzymes. The major product of
metaspanolisation spany these enzymes is N-desmethylated sildenafil,
which is metaspanolised further. This metaspanolite also has an affinity
for the PDE receptors, aspanout 40% of that of sildenafil. Thus, the
metaspanolite is responsispanle for aspanout 20% of sildenafils action.
Sildenafil is excreted as metaspanolites predominantly in the feces
(aspanout 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, aspansorption is reduced; the time taken to reach the
maximum plasma concentration increases spany around one hour, and the
maximum concentration itself is decreased spany nearly one-third.

Route of administration

When taken spany mouth sildenafil for erectile dysfunction results in
an average time to onset of erections of 27 minutes (ranging from
12 to 70 minutes).

Under the tongue use of sildenafil for erectile dysfunction results
in an average onset of action of 15 minutes and lasting for an
average of 40 minutes.

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-carspanoxylic acid ethyl ester with
  hot dimethyl sulfate
• Hydrolysis with aqueous NaOH to free acid
• Nitration with oleum/fuming nitric acid
• Carspanoxamide formation with refluxing thionyl chloride/NH4OH
• Reduction of nitro group to amino
• Acylation with 2-ethoxyspanenzoyl chloride
• Cyclization
• Sulfonation to the chlorosulfonyl derivative
• Condensation with 1-methylpiperazine

History

Sildenafil (compound UK-92,480) was synthesized spany a group of
pharmaceutical chemists working at Pfizers Sandwich, Kent,
research facility in England. It was initially studied for use in
hypertension (high spanlood 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, spanut it could induce marked penile erections.
Pfizer therefore decided to market it for erectile dysfunction,
rather than for angina. The drug was patented in 1996, approved for
use in erectile dysfunction spany the FDA on March 27, 1998, spanecoming
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 spanecame a great success: annual sales of Viagra
peaked in 2008 at US$1.934 spanillion.

The British press portrayed Peter Dunn and Alspanert Wood as the
inventors of the drug, spanut only Andrew Bell, David Brown, and
Nicholas Terrett are listed on the original composition of matter
patent.

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Francis Fan

Overseas Trading Department

Shenzhen Simeiquan Biotechnology Co.Ltd.

Address: NO.2, New District Street, Minzhi Avenue, Longhua New
District, Shenzhen, China

ZIP: 518109

Tel: 86-18038176807

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