[Molecular cardiopharmacology of selective inhibitors of cyclic nucleotide phosphodiesterase isozymes].

Abstract

The existence of multiple isozymes of cyclic nucleotide phosphodiesterase (PDE) in many tissues including the heart has been demonstrated. Five isozyme families, each composed of several subtypes and having different tissue and subcellular distributions, have been characterized. Selective inhibitors of PDE III (cGMP-inhibited PDE) elevates the cAMP level which mediates positive inotropic actions with compartmentation of cAMP related to cardiac cell particulate structures. Both cardiac cytosolic and particulate PDE III were potently and selectively inhibited by the new cardiotonic agents competitively with respect to cAMP, except for vesnarinone. There might be at least two subtypes of PDE III, and vesnarinone may be a selective subtype inhibitor of PDE III in human heart. It was also reported that vesnarinone was beneficial in treating patients with congestive heart failure. Moreover, selective inhibitors of PDE III with ancillary properties such as calcium sensitization may prove to be more useful drugs for the treatment of heart failure.

• Authors: T Tanaka, J Mukai, M Naka
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 100 Issue 3 Pg. 249-58 (Sep 1992) ISSN: 0015-5691 [Print] Japan
• PMID: 1328001 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Isoenzymes
• 2',3'-Cyclic-Nucleotide Phosphodiesterases

Topics

• 2',3'-Cyclic-Nucleotide Phosphodiesterases (antagonists & inhibitors)
• Animals
• Cattle
• Guinea Pigs
• Humans
• Isoenzymes (antagonists & inhibitors)
• Myocardium (enzymology)
• Tissue Distribution