Phosphodiesterases (PDEs) are enzymes that convert cyclic nucleotides (cAMP and cGMP) to their corresponding 5′-AMP and 5′-GMP in order to inactivate the cyclic nucleotides. There are currently 11 members in the PDE superfamily. PDE1-3, 5, 6, and 9-11 can hydrolyze cGMP. Cyclic GMP stimulates PDE2 and 5 activities but inhibits PDE3 activity. PDEs have similar structures, and, in some cases, more than one PDE subtype can be expressed in a single cell. Each PDE subtype has a unique subcellular localization. Thus, PDEs play a key role in regulating intracellular levels of the second messengers cAMP and cGMP, and hence cell function.

PDE4, formerly known as cAMP-PDE, is a cAMP-specific PDE and is the predominant isoenzyme in the majority of inflammatory cells, implicated in inflammatory airways disease. It exists in the airways smooth muscle, brain and cardiovascular tissues. Importantly, PDE4 is the largest PDE subfamily with over 35 different isoforms. PDE4 is predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system. Therefore, PDE4 is an important target for research airway diseases, psoriatic arthritis, and atopic dermatitis. In addition, PDE4 inhibitors show antidepressant and memory enhancement activities.

Rolipram is a selective PDE4 inhibitor.

Rolipram, a potant and selective PDE4 inhibitor, can inhibit all PDE4 isoforms A, B, C and D. In the early 1970s, studies have shown that elevation of cAMP could enhance noradrenergic neurotransmission in the central nervous system. Therefore Rolipram was developed as a potential drug to research depression. Rolipram enhances tissue protection, anatomical repair and functional recovery. It functions as an antidepressant, stimulates neurite outgrowth and axonal regeneration in the presence of myelin inhibitors. Effects of rolipram on acquisition improved both long-term memory during a 24-h interval and short-term memory after a 1-h interval in a scopolamine-deficit model.

All in all, Rolipram, a selective PDE4 inhibitor, can inhibit PDE4A, PDE4B, PDE4C, and PDE4D.


Boswell-Smith V, et, al. Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S252-7.