A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions

Phosphodiesterase type 5 (PDE5) is a cyclic GMP (cGMP) specific protein. It hydrolyzes the phosphodiesterase linkage and catalyzes the conversion of cGMP to 5’ GMP, which controls different physiological activities of the body. PDE5 is associated with biomedical conditions like neurological disorders, pulmonary arterial hypertension, cardiomyopathy, cancer, erectile dysfunction, and lower urinary tract syndrome. Inhibition of PDE5 has now been proven pharmaceutically effective in a variety of therapeutic conditions. Avanafil, tadalafil, sildenafil, and vardenafil are the most commonly used PDE5 inhibitors (PDE5i) today which are often used for the management of erectile dysfunction, lower urinary tract syndromes, malignancy, and pulmonary arterial hypertension. However, these synthetic PDE5i come with a slew of negative effects. Some of the most common side effects include mild headaches, flushing, dyspepsia, altered color vision, back discomfort, priapism, melanoma, hypotension and dizziness, non-arteritic anterior ischemic optic neuropathy (NAION), and hearing loss. In light of the potential negative effects of this class of medications, there is a lot of room for new, selective PDE5 inhibitors to be discovered. We have found 25 plant botanical compounds effectively inhibiting PDE5 which might be useful in treating a variety of disorders with minimal or no adverse effects.

Role of Phosphodiesterase Type 5 Inhibitor on Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms / 대한남성과학회지

There is strong evidence from multiple epidemiological studies that benign prostate hyperplasia (BPH) induced lower urinary tract symptoms (LUTS) are correlated with erectile dysfunction (ED). Although a direct causal relationship is not established yet, four pathophysiological mechanisms can explain the relationship. These include alteration in activity of nitric oxide (NO)-cyclic GMP signal pathway, autonomic hyperactivity, increased Rho kinase/Rho A pathway and pelvic atherosclerosis. Androgens have been suggested to have an important role in the maintenance of the functional and structural integrity of the urinary tract. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. Sildenafil is a pioneer of this clinical trial and appears to improve both erectile function and LUTS in subjects with ED. Basically PDE5 I with long half life is an appropriate candidate, therefore tadalafil and undenafil had been used to evaluate both diseases. Placebo-controlled trials of tadalafil showed improvement of LUTS secondary to BPH, but none of the studies showed a significant effect on urodynamic measures. PDE5 Is, such as sildenafil and tadalafil, increase the concentration of cGMP in plasma and smooth muscle, facilitating erection of the penis, relaxation of the bladder neck and prostate and subsequent bladder emptying. And theses PDE5 Is increase cAMP and cGMP levels and are more highly distributed in the prostate than plasma. These findings may help in the assessment of the feasibility of using PDE5 Is to concurrently treat both LUTS and ED.