Inhibition of calmodulin-dependent cyclic nucleotide phosphodiesterase by flunarizine, a calcium-entry blocker

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Abstract

It has been reported that flunarizine, classified as calcium entryblockers, is a potent brain protective drug without any heart depressant effect, contrasting with other drugs in this group. This paper presents evidence that through a competitive antagonism against calmodulin, a major intracellular calcium receptor, flunarizine inhibits the calcium·calmodulin-activated phosphodiesterase activity of bovine brain, but not of heart, whereas other calcium-entry blockers and calmodulin antagonists inhibit to the same extent, the activation of the enzyme from the two sources. It could be suggested that some of pharmacological effects by flunarizine and its differences from other calcium-entry blockers may be explained by its interaction with calmodulin.

References (16)

  • H.C. Ho et al.

    Biochem. Biophys. Acta

    (1976)
  • R.W. Butcher et al.

    J. Biol. Chem

    (1962)
  • N. Sakamoto et al.

    Biochem. Pharmacol

    (1978)
  • A. Fleckenstein

    Ann. Rev. Pharmacol. Toxicol

    (1977)
  • J.M. Van Nueten et al.
  • M. Spedding

    Naunyn-Schmiedeberg's Arch Pharmacol

    (1982)
  • S.-L. Boström et al.

    Nature

    (1981)
  • H. Metzger et al.

    Arzneim.-Forsch

    (1982)
There are more references available in the full text version of this article.

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