Therapeutic potential of cyclic nucleotide phosphodiesterase inhibitors in heart failure

Expert Opin Investig Drugs. 2000 May;9(5):963-73. doi: 10.1517/13543784.9.5.963.

Abstract

There are several reasons to believe that agents that augment cAMP-mediated signalling in cardiac myocytes should have beneficial effects in patients with heart failure. However, clinical trials of first-generation cyclic nucleotide phosphodiesterase (PDE3) inhibitors, which raise cAMP content by blocking its hydrolysis, have shown that chronic administration of these drugs affect survival adversely. The problem may be the non-selective activation of a broad spectrum of cAMP-regulated cellular responses these agents elicit. More selective (or alternatively selective) cyclic nucleotide PDE inhibitors might improve results by evoking a more restricted set of cellular responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Animals
  • Cyclic AMP / metabolism
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Humans
  • Phosphodiesterase Inhibitors / therapeutic use*

Substances

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