What is Sildenafil ?Admin
Sildenafil is a selective and competitive inhibitor of type 5 phosphodiesterases (PDE5) on smooth muscle cells in the penis and pulmonary vessels.
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Sildenafil is a selective phosphodiesterase type 5 (PDE5) inhibitor that is more potent than other phosphodiesterases.
In animal research, it produces mild decreases in systolic and diastolic blood pressure. These two main actions result in the improvement of erectile dysfunction and pulmonary arterial hypertension in the animal subjects.
STRUCTURE OF SILDENAFIL
Molecular Formula: C28H38N6O11S
Molecular weight: 666.7 g/mol
CAS number: 171599-83-0
IUPAC Name: 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one;2-hydroxypropane-1,2,3-tricarboxylic acid.
MECHANISM OF ACTION
Sildenafil has shown vasodilating and potential anti-inflammatory activities in studies.
Its mechanism of action shows it selectively targets and inhibits cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), thereby inhibiting the PDE5-mediated degradation of cGMP found in smooth muscle in animal subjects.
It results in prolonged smooth muscle relaxation in the corpus cavernosum of the penis of animal test subjects, thereby causing vasodilation, blood engorgement, and a prolonged penile erection.
Also, in the smooth muscle of the pulmonary vasculature of animals, it causes smooth muscle relaxation, vasodilation of the pulmonary vascular bed, relieving pulmonary hypertension, and increasing blood flow in the lungs of test subjects.
Across trials in animal test subjects, sildenafil demonstrated different benefits. They include the following:
- It improves erectile dysfunction by inhibiting phosphodiesterase-5.
- It is beneficial in managing pulmonary arterial hypertension by causing vasodilation in the pulmonary vasculature.
- It increases bladder and prostate tissue oxygenation, improving benign prostatic hyperplasia.
- It exhibits anti-amnesic activity against intracerebroventricular streptozotocin-induced memory loss and vascular dementia in the experimental animals. Also, sildenafil improves cognitive function in animals with hepatic encephalopathy.
- Studies have provided evidence that sildenafil delays the progression of heart failure and reverses cardiac remodeling in animal models.
- It improves endothelial function and placental perfusion in preeclamptic patients.
- It reduces inflammatory cytokines in serum and bronchoalveolar lavage fluid of animal models.
- It induces changes in liver mitochondrial protein dynamics, restoring the redox homeostasis and contributing to potential hepato-protection.
- It is effective in treating lower urinary tract symptoms.
- It may treat alopecia.
SILDENAFIL SIDE EFFECTS
Common side effects in animal studies include:
- Dyspepsia of mild or moderate severity.
- Myalgia that occurs frequently.
- An abnormal vision.
- Headache and vasodilatation.
- Hypotension and dizziness.
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- National Center for Biotechnology Information. PubChem Database. Sildenafil citrate, CID=135413523, https://pubchem.ncbi.nlm.nih.gov/compound/Sildenafil-citrate (accessed on Dec. 8, 2019)
- Corbin JD. Mechanisms of action of PDE5 inhibition in erectile dysfunction. Int J Impot Res. 2004;16 Suppl 1:S4–S7. doi:10.1038/sj.ijir.3901205
- Boolell M et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996; 8: 47–52.
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Sildenafil. [Updated 2017 Aug 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548510/
- Chuang T, Strauss JD, Murphy RA, Steers WD. Sildenafil, a type-5 cGMP phosphodiesterase inhibitor, specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro. J Urol 1998; 160: 257–261.