Therapeutic benefits of Phosphodiesterase type 5 inhibitors: A comprehensive review

Phosphodiesterase type 5 (PDE5) inhibitors have been widely used to treat erectile dysfunction. This review aims to explore the favorable effects of PDE5 inhibitors in clinical applications beyond their conventional use. There is growing evidence highlighting PDE5 inhibitors benefits in a wide range of different systemic conditions, such as benign prostatic hyperplasia, lower urinary tract symptoms, and pulmonary arterial hypertension. The positive outcomes of PDE5 inhibitors are mainly mediated through nitric oxide/ cyclic guanosine monophosphate signaling pathway activation. PDE5 inhibitors were shown to possess anti-oxidant properties, anti-inflammatory activity, and anti-apoptotic properties. In addition, PDE5 inhibitors have been documented as neuroprotective agents in different animal models. Thus, we will discuss the prominent role of PDE5 inhibitors against neurodegenerative disorders with primary concern on Alzheimer's disease, cerebral ischemia, depression, and Parkinson’s disease. Current treatment options for neurodegenerative diseases only provide symptomatic relief and can't achieve complete protection against the disease progression. Our review is based on evidence from pre-clinical studies and epidemiological studies that elucidate the underlying mechanisms suggesting the potential benefits of PDE5 inhibitors.