Which enzyme family is targeted by tadalafil?

• A. PDE1
• B. PDE3
• C. PDE5
• D. PDE9

Answer: (C)

Tadalafil works by inhibiting the enzyme PDE5. In penile tissue, sexual stimulation triggers the release of nitric oxide, which activates guanylate cyclase to raise the levels of cGMP. This cGMP causes smooth muscle relaxation in the erectile tissue, allowing more blood to fill the penis and produce an erection. PDE5 normally breaks down cGMP, so blocking PDE5 sustains higher cGMP levels and enhances the erectile response in the presence of sexual arousal. Tadalafil is selective for PDE5, meaning it preferentially inhibits this enzyme over other phosphodiesterases found in different tissues (like PDE1, PDE3, PDE6, etc.), which helps limit off-target effects. The result is improved erectile function driven by the NO-cGMP pathway, specifically through PDE5 inhibition.