Sildenafil
[CAS# 139755-83-2]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Treatment of male erectile dysfunction drugs
• Name: Sildenafil
• Synonyms: 5-[2-Ethoxy-5-(4-methylpiperazin-1-yl-sulphonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazol[4,3d]pyrimidin-7-one
• Molecular Formula: C₂₂H₃₀N₆O₄S
• Molecular Weight: 474.58
• CAS Registry Number: 139755-83-2
• EC Number: 604-158-7
• SMILES: CCCC1=NN(C2=C1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H319-H412
• Safety Statements: P264-P264+P265-P270-P273-P280-P301+P317-P305+P351+P338-P330-P337+P317-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

Sildenafil was originally synthesized by the pharmaceutical company Pfizer and was discovered during research into potential treatments for high blood pressure and angina. However, during clinical trials in the 1990s, researchers observed an unexpected side effect on penile erections. This discovery led to the recognition of sildenafil's potential as a treatment for erectile dysfunction (ED). In 1998, it became the first oral medication approved by the FDA for the treatment of ED, revolutionizing the treatment of this condition and improving the lives of millions of men worldwide.

Sildenafil is primarily used to treat erectile dysfunction, a common condition characterized by the inability to achieve or maintain a penile erection sufficient for sexual activity. It works by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which regulates blood flow to the penis. By blocking PDE5, sildenafil promotes relaxation of smooth muscle cells and vasodilation of the penile arteries, thereby increasing blood flow and improving erectile function.

Sildenafil is also approved for the treatment of pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs. In PAH, sildenafil acts as a vasodilator, reducing pulmonary vascular resistance and improving exercise capacity. It helps relieve symptoms such as shortness of breath and fatigue, improving patients' quality of life.

Sildenafil also shows promise in treating Raynaud's phenomenon, a condition characterized by spasm of peripheral arterial vessels, resulting in reduced blood flow to the fingers and toes. By promoting vasodilation and improving blood circulation, sildenafil can help relieve symptoms such as numbness, pain, and color changes in the extremities associated with Raynaud's phenomenon.

Studies have explored the potential of sildenafil in preventing and treating altitude sickness, also known as acute mountain sickness (AMS). By increasing pulmonary artery pressure and improving oxygenation, sildenafil helps relieve symptoms such as headache, nausea, and fatigue that occur in people at high altitudes. However, further studies are needed to determine its effectiveness and safety in this setting.

In addition to its approved indications, sildenafil is sometimes used to treat other conditions such as female sexual arousal disorder, antidepressant-induced sexual dysfunction, and idiopathic pulmonary fibrosis. Although evidence supporting these uses is limited, sildenafil's mechanism of action and vasodilatory effects suggest efficacy in certain patient populations.

References

2000. Long-term efficacy and safety of oral Viagra® (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal. International Journal of Impotence Research.
DOI: 10.1038/sj.ijir.3900527

2003. PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers. Hypertension (Dallas, Tex. : 1979).
DOI: 10.1161/01.hyp.0000068202.42431.cc

2000. Effect of sildenafil on coronary active and reactive hyperemia. American journal of physiology. Heart and circulatory physiology.
DOI: 10.1152/ajpheart.2000.279.5.h2319