Preferential inhibition of human phosphodiesterase 4 by ibudilast.
Article Details
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Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K
Preferential inhibition of human phosphodiesterase 4 by ibudilast.
Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28.
- PubMed ID
- 16313925 [ View in PubMed]
- Abstract
Ibudilast ophthalmic solution exhibited an improved clinical efficacy over cromoglycate in the treatment of allergic conjunctivitis. To further characterize its principal mode of action, the phosphodiesterase (PDE) inhibitory profile of ibudilast has been examined using human recombinant enzymes. Ibudilast, but not the other commonly used anti-allergic ophthalmic solutions including cromoglycate, ketotifen, tranilast and levocabastine, potently inhibits purified human PDE4A, 4B, 4C and 4D with IC50 values at 54, 65, 239 and 166 nM, respectively. Ibudilast effectively blocks lipopolysaccharide (LPS)-induced tumor necrosis factor (TNFalpha, IC50 = 6.2 microM) and N-formyl-Met-Leu-Phe (fMLP)-induced leukotriene (LT) B4 biosynthesis (IC50 = 2.5 microM) in human whole blood, which are 3 and 6-fold more potent than cilomilast, respectively. The attenuated inflammatory and allergic responses from the potent and preferential PDE4 inhibition of ibudilast may have contributed significantly to its beneficial pharmacological responses and distinguishes ibudilast from the other ophthalmic solutions in the treatment of ocular allergy.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Ibudilast cAMP-specific 3',5'-cyclic phosphodiesterase 4A Protein Humans YesInhibitorDetails Ibudilast cAMP-specific 3',5'-cyclic phosphodiesterase 4B Protein Humans YesInhibitorDetails Ibudilast cAMP-specific 3',5'-cyclic phosphodiesterase 4C Protein Humans YesInhibitorDetails Ibudilast cAMP-specific 3',5'-cyclic phosphodiesterase 4D Protein Humans UnknownInhibitorDetails - Drug Interactions
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