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

Abstract

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.