Which statement best describes the mechanism of action of tadalafil?

• A. Inhibits PDE3, leading to increased cAMP.
• B. Activates guanylyl cyclase, increasing cGMP.
• C. Binds to active sites of PDE5, blocks hydrolysis of cGMP, maintains high cGMP levels.
• D. Blocks calcium channels in vascular smooth muscle.

Answer: (C)

Selective inhibition of PDE5 is the key. Tadalafil binds to the active site of phosphodiesterase-5, blocking the hydrolysis of cGMP. After sexual stimulation, nitric oxide releases and stimulates guanylate cyclase to raise cGMP. By preventing cGMP breakdown, tadalafil keeps cGMP levels high, which activates protein kinase G, lowers intracellular calcium, and relaxes smooth muscle in the corpora cavernosa. This relaxation increases blood flow and produces an erection. The drug’s selectivity for PDE5 explains why it boosts the NO–cGMP pathway rather than increasing cAMP (PDE3 action), directly activating guanylate cyclase, or blocking calcium channels.