Relationship between inotropic activity and phosphodiesterase inhibition for flosequinan and milrinone

Ronald E. Weishaar, Mary L. Kirker, Annette M. Wallace, Victor A. Ferraris, Lewis W. Britton, Malcolm F. Sim

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The goal of this study was to assess the relationship between the positive inotropic response to high concentrations of the vasodilators flosequinan and BTS 53 554 (the sulfone metabolite of flosequinan) and the effect of both compounds on different forms of cyclic nucleotide phosphodiesterase. In addition, the relationship between inotropic activity and phosphodiesterase inhibition for the cardiotonic milrinone was also evaluated. All three agents exerted a positive inotropic effect on human cardiac muscle fibers. The concentration of milrinone required to increase cardiac contractility was comparable to the concentration required to inhibit the milrinone-sensitive subclass of cyclic AMP-specific phosphodiesterase (type III phosphodiesterase). However, no such relationship was observed for flosequinan and BTS 53 554. These results suggest that the cardiac response to high concentrations of flosequinan and BTS 53 554 is not mediated by inhibition of type III phosphodiesterase.

Original languageEnglish
Pages (from-to)363-366
Number of pages4
JournalEuropean Journal of Pharmacology
Volume236
Issue number3
DOIs
StatePublished - Jun 4 1993

Keywords

  • (Human)
  • Cardiac muscle
  • Contractility
  • Flosequinan
  • Heart failure
  • Phosphodiesterase

ASJC Scopus subject areas

  • Pharmacology

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