Clinical Implication of Phosphodiesterase-4-Inhibition

Int J Mol Sci. 2022 Jan 21;23(3):1209. doi: 10.3390/ijms23031209.

Abstract

The pleiotropic function of 3',5'-cyclic adenosine monophosphate (cAMP)-dependent pathways in health and disease led to the development of pharmacological phosphodiesterase inhibitors (PDE-I) to attenuate cAMP degradation. While there are many isotypes of PDE, a predominant role of PDE4 is to regulate fundamental functions, including endothelial and epithelial barrier stability, modulation of inflammatory responses and cognitive and/or mood functions. This makes the use of PDE4-I an interesting tool for various therapeutic approaches. However, due to the presence of PDE4 in many tissues, there is a significant danger for serious side effects. Based on this, the aim of this review is to provide a comprehensive overview of the approaches and effects of PDE4-I for different therapeutic applications. In summary, despite many obstacles to use of PDE4-I for different therapeutic approaches, the current data warrant future research to utilize the therapeutic potential of phosphodiesterase 4 inhibition.

Keywords: PDE; PDE4-I; phosphodiesterase; phosphodiesterase-4; phosphodiesterase-inhibitors.

Publication types

  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Animals
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / enzymology
  • Cyclic AMP / metabolism*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / enzymology
  • Mood Disorders / drug therapy*
  • Mood Disorders / enzymology
  • Phosphodiesterase 4 Inhibitors / pharmacology*

Substances

  • Phosphodiesterase 4 Inhibitors
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases