Agents and Actions

, Volume 17, Issue 2, pp 192–196 | Cite as

Cyclic nucleotide phosphodiesterase inhibition by a benzoic acid derivative

  • John J. F. Killackey
  • Barbara A. Killackey
  • Richard B. Philp
Immunosuppression and Inflammation

Abstract

Acetylsalicylic acid (ASA) and three structurally related benzoic acid derivatives, 2-acetylbenzoic acid (ABA), 3-methylphthalide (3-MP), and 3-hydroperoxy-3-methylphthalide (3-HMP), were tested for inhibitory effects on three human blood platelet cyclic nucleotide phosphodiesterase (PDE) activities. 3-MP caused a dose-dependent inhibition of the high and low affinity cyclic AMP PDE activities and the cyclic GMP PDE activity. 3-HMP had some inhibitory effects but only on the low affinity cyclic AMP PDE activity. ASA and ABA had no effects. This study shows that progressive structural changes in the ASA molecule can shift the pharmacological profile from a cyclooxygenase inhibitor (ASA) to an inactive compound (ABA) to a PDE inhibitor (3-MP) and back again to a cyclooxygenase inhibitor (3-HMP). It is proposed that the potent anti-inflammatory effects of 3-MP, which differ from those of ASA, are mediated through the inhibition of the cyclic nucleotide PDE system.

Keywords

Acetylsalicylic Acid Cyclic Nucleotide Phosphodiesterase Inhibition Cyclooxygenase Inhibitor Inactive Compound 

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Copyright information

© Birkhäuser Verlag 1985

Authors and Affiliations

  • John J. F. Killackey
    • 1
  • Barbara A. Killackey
    • 1
  • Richard B. Philp
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of Western OntarioLondon

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