Chemistry
10th Edition
ISBN:9781305957404
Author:Steven S. Zumdahl, Susan A. Zumdahl, Donald J. DeCoste
Publisher:Steven S. Zumdahl, Susan A. Zumdahl, Donald J. DeCoste
Chapter1: Chemical Foundations
Section: Chapter Questions
Problem 1RQ: Define and explain the differences between the following terms. a. law and theory b. theory and...
Related questions
Question
Viagra inhibit PDE5?what does it means?what will happen if Viagra inhibit PDE5?

Transcribed Image Text:Silverman &
Holladay
Discovery of Drugs through Clinical Observations
The impotence drug sildenafil citrate (Viagra) was designed for the treatment of angina and
hypertension by blocking the enzyme phosphodiesterase-5, which hydrolyzes cyclic guanosine
monophosphate (CGMP), a vasodilator that allows increased blood flow.
In 1991, sildenafil went into Phase I clinical trials for angina. In Phase II clinical trials, it was not as
effective against angina as Pfizer had hoped, so it went back to Phase I clinical trials to see how
high of a dose could be tolerated. It was during that clinical trial that the volunteers reported
increased erectile function.
Given the weak activity against angina, it was an easy decision to try to determine its effectiveness
as the first treatment for erectile dysfunction.
Sildenafil works by the mechanism for which it was designed as an antianginal drug, except it
inhibits the phosphodiesterase in the penis (phosphodiesterase-5) as well as the one in the heart.
Sexual stimulation causes release of nitric oxide in the penis. Nitric oxide is a second
messenger molecule that turns on (pun intended) the enzyme guanylate cycla
converts guanosine triphosphate to CGMP.
NO
L-Arg
Nitric oxide
,which
Synthase
Stimulates
Erection
Guanylate cyclase
Increased
blood
flow
The vasodilator relaxes the smooth muscle in the
corpus cavernosum, allowing blood to flow into
the penis, thereby producing an erection.
GTP
Smooth
CGMP-
muscle
relaxation
GMP Vasoconstriction
PDE 5
However, phosphodiesterase-5 (PDE-5) hydrolyzes the CGMP, which
causes vasoconstriction and the outflow of blood from the penis.
Sildenafil inhibits this phosphodiesterase, preventing the hydrolysis of
CGMP and prolonging the vasodilation effect.
Inhibits
Viagra
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