Phophodiesterase-4 enzyme inhibitors as potential anti-inflammatory agents
Journal Title: Innovations in Pharmaceuticals and Pharmacotherapy (IPP) - Year 2015, Vol 3, Issue 2
Abstract
The Phosphodiesterases (PDEs) are a diverse family of enzymes that hydrolyze cyclic nucleotides such as cAMP & cGMP to the inactive 5’-AMP and 5’-GMP, respectively and thus play a key role in regulating intracellular levels of these second messengers and hence modulate cell functions which regulate a number of cellular processes such as metabolism, cell proliferation and differentiation, secretion, vascular and airway smooth muscle relaxation & the release of inflammatory mediators. The PDE superfamily contains 11 PDE isoenzymes (PDE1 to PDE11), which differ in primary structures, affinities for cAMP and cGMP, responses to specific effectors, sensitivities to specific inhibitors and mechanism of regulation. Each isoenzyme possesses at least one subtype. PDE4 has mainly four subtypes i.e. PDE4a, PDE4b, PDE4c, and PDE4d. The development of selective PDE4b inhibitors has not gained success till yet because of the structural similarity between the two isoforms of PDE4 i.e. PDE4b & PDE4d. Inhibition of PDE4b is responsible for the therapeutic effect while that of PDE4d for the side effects. The present review will be focused on the selective PDE4 enzyme inhibitors & their potential therapeutic utility
Authors and Affiliations
Amit Girdhar
Keywords
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