AVANAFIL POTENTIAL SIDE EFFECTS AND BENEFITS
zhion@zhion.com    November 21, 2005
WHAT IS AVANAFIL? WHAT IS ITS ADVANTAGE?
Avanafil, a PDE5 inhibitor, blocks the activity of a protein that prevents blood
vessels from expanding. According to the news, avanafil is better at
concentrating its activity on PDE5 than other drugs in its class.

Examples of type V (5) phosphodiesterase inhibitors include, but not limited to,
sildenafil, tadalafil, vardenafil, avanafil, zaprinast RTM, papaverine and
dipyridamole. Other type 5 PDE inhibitors are disclosed in PCT Publication Nos.
WO 94/28902, WO 96/16644, U.S. Pat. No. 6,338,862 and U.S. Pat. No.
6,476,037.

Avanafil's great advantage is that it acts faster than the other PDE5 inhibitors,
taking effect in about 30 minutes, and disappears from the body faster.
Because of the fast action, those men who use it won't have to wait as long.

Avanafil's relatively quick disappearance from the bloodstream should lessen its
possible side effects. In a study of 295 men, the effectiveness was "excellent,
while the side effects were minimal, according to the news release.

WHAT ARE PDE INHIBITORS?
Phosphodiesterase (PDE) inhibitors are a class of intracelleular enzymes which
mediate the catabolism of second messengers like cyclic adenosine
monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These
enzymes have been classified into at least eleven groups (types I-XI) and
various subclasses based on their amino acid sequence and substrate specificity
(Polson, 1996; Trophy, 2000). The various PDE differ in their tissue, cellular
distribution, and their specificity towards cAMP or cGMP. (table 1). So
phosphodiesterase inhibitors have applications in a number of disorders
including vascular, neuronal and inflammatory disorders (Zang 2002, Martin
2002, Grootendorst 2002, Burnouf, 2002). PDE inhibitors are drug candidates
for the treatment of a number of disorders including heart failure, depression,
asthma, inflammation, sexual dysfunction, and erectile dysfunction.
Phoshodiesterase 4D has been shown to have a role in ischemic stroke
(Gretarsdottir, 2003). [1]

WHAT ARE THE POTENTIAL APPLICATIONS OF Phosphodiesterase PDE5
INHIBITORS?
1. Enhance sexual function in men following prostate surgery.
2. Enhance sexual function in hypogonadal men by combining testosterone and
phosphodiesterase inhibitor.
3. Treatment of premature or rapid ejaculation.
4. Enhance sexual function in women
5. Enhance endothelial function in patients with primary pulmonary hypertension.
6. Treatment of urinary tract symptoms due to benign prostatic hyperplasia.
7. Treatment of urinary incontinence.
8. Treatment of sickle cell anemia by combination therapy with hydroxyurea
9. Enhance sexual function in men and women by combination therapy with
antioxidants, vitamin E, arginine, apomorphine , dopamine agonists, alpha
adrenergic blocker etc.
10. Prevention and treatment of stroke.
11. Treatment of coronary and cerebral vascular diseases.
12. Treatment of thrombosis
13. Treatment of ocular hypertension
14. Treatment of pregnancy-induced hypertension.
15. Treatment of anal sphincter disorders (Jones, 2002).
16. Treatment of neurodegenerative diseases such as Alzheimer's disease,
Parkinson's disease, amyloid diseases, Prion diseases.
17. Treatment of other diseases where cGMP is implicated to have beneficial
effects.

WHAT ARE THE SIDE EFFECTS OF AVANAFIL?
Not much information has been reported about avanafil side effects. In general,
the side effects of Phosphodiesterase inhibitors include hypotension, flushing,
headache, nasal congestion and heartburn and these effects are dose
dependent (Moreira, 2000). The incidence of cardiovascular events and deaths
have been reported with the use of PDE 5 inhibitors (Lim, 2002). This may be
due to the fact that PDE5 inhibitors dilate the coronary arteries which makes
the patient feel better. This may lead to vigorous physical activity (exercise or
intercourse). Such activity may lead to ischemia and heart attack. Also
interaction with other drugs including nitroglycerine poses substantial risks. The
visual side effects of Phosphodiesterase 5 inhibitors are due to the inhibition of
Phosphodiesterase 6 found in the retina. [1]

ABOUT ERECTILE DYSFUNCTION
Erectile dysfunction, sometimes called "impotence," is the repeated inability to
get or keep an erection firm enough for sexual intercourse. The word
"impotence" may also be used to describe other problems that interfere with
sexual intercourse and reproduction, such as lack of sexual desire and problems
with ejaculation or orgasm. Using the term erectile dysfunction makes it clear
that those other problems are not involved.

Erectile dysfunction can be a total inability to achieve erection, an inconsistent
ability to do so, or a tendency to sustain only brief erections. These variations
make defining erectile dysfunction  and estimating its incidence difficult.
Estimates range from 15 million to 30 million, depending on the definition used.
According to the National Ambulatory Medical Care Survey (NAMCS), for every
1,000 men in the United States, 7.7 physician office visits were made for erectile
dysfunction  in 1985. By 1999, that rate had nearly tripled to 22.3. The
increase happened gradually, presumably as treatments such as vacuum
devices and injectable drugs became more widely available and discussing
erectile function became accepted. Perhaps the most publicized advance was the
introduction of the oral drug sildenafil citrate (Viagra) in March 1998. NAMCS
data on new drugs show an estimated 2.6 million mentions of Viagra at
physician office visits in 1999, and one-third of those mentions occurred during
visits for a diagnosis other than erectile dysfunction.

In older men, erectile dysfunction   usually has a physical cause, such as
disease, injury, or side effects of drugs. Any disorder that causes injury to the
nerves or impairs blood flow in the penis has the potential to cause erectile
dysfunction  . Incidence increases with age: About 5 percent of 40-year-old
men and between 15 and 25 percent of 65-year-old men experience erectile
dysfunction  . But it is not an inevitable part of aging.

ABOUT VIVUS INC.
VIVUS, Inc. was founded in 1991 by Virgil A. Place, M.D., to research, develop
and commercialize therapies to restore male sexual function.  VIVUS' first
product, MUSE®, was based on the discovery that certain vasodilating agents,
some of which are used to treat hypertension, can be applied in the urethra and
absorbed into the erectile tissues, causing an erection in males. Today, VIVUS
continues to develop innovative therapies to restore male sexual function and is
at the forefront of pioneering therapies for women's sexual health.

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SOURCES
VIVUS Announces Presentation of Positive Results From Five Key
Avanafil Studies at the Sexual Medicine Society Fall Meeting Press Release Nov.
18 2005 National Institute of Diabetes and Digestive and Kidney Diseases
[1] Methods and compositions to enhance the efficacy of phosphodiesterase
inhibitors  US PATENT APPLICATION NUMBER 20050009835
AVANAFIL POTENTIAL BENEFITS
Avanafil (made by Vivus Inc.) may be a potentially faster-acting competitor on the horizon for Viagra (and Levitra
and Cialis) in the battle against impotence. It could be marketed by about 2007, if it can enter the Phase III study
next year.