The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family

Eur J Pharmacol. 2006 May 24;538(1-3):39-42. doi: 10.1016/j.ejphar.2006.02.053. Epub 2006 Mar 13.

Abstract

Ibudilast is widely used in Japan to treat ischemic stroke and bronchial asthma. Its mode of action is through the inhibition of cyclic nucleotide phosphodiesterases (PDEs). Growing evidence suggests this compound has utility in a range of neurological conditions linked to its ability to elevate cellular cyclic nucleotide concentrations, however limited data exists on Ibudilast's action on individual PDE families. We therefore used an extensive panel of human PDE enzymes to define the PDE inhibitory profile of this compound. Ibudilast preferentially inhibits PDE3A, PDE4, PDE10 and PDE11 with lesser inhibition of a number of other families. The significance of these findings is discussed in relation to Ibudilast's observed effects on certain disease states.

MeSH terms

  • Animals
  • Cell Line
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Humans
  • Hydrolysis / drug effects
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kinetics
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyridines / pharmacology*
  • Spodoptera
  • Substrate Specificity

Substances

  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Pyridines
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • Cyclic GMP
  • ibudilast