phosphodiesterase inhibitor phosphodiesterase inhibitor a phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (pde), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (camp) and cyclic guanosine monophosphate (cgmp) by the respective pde subtype(s). the ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, the actions in the heart, and lungs being some of the first to find a therapeutic use. phosphodiesterase-5 history the different forms or subtypes of phosphodiesterase were initially isolated from rat brains in the early 1970s and were soon afterward shown to be selectively inhibited in the brain and in other tissues by a variety of drugs. the potential for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by weiss and hait. this prediction meanwhile has proved to be true in a variety of fields. classification