PMID: 9635162Jun 23, 1998Paper

Effects of a selective phosphodiesterase IV inhibitor (CDP-840) in a leukotriene-dependent non-human primate model of allergic asthma

Canadian Journal of Physiology and Pharmacology
T R JonesI W Rodger

Abstract

The activity of CDP-840, a novel, selective phosphodiesterase IV inhibitor was determined in a leukotriene-dependent non-human primate model of allergic asthma. Measurements of specific airway resistance (sRaw) were recorded in a dual chamber plethysmograph for 1 h and 3-5 h after challenge of allergic conscious squirrel monkeys with an aerosol of ascaris antigen. Orally administered CDP-840 (10 mg/kg; 1 h before challenge) produced partial inhibition (41 and 45%, respectively) of both the acute (1 h post antigen) response and the late (3-5 h post antigen) response to antigen but failed to alter the response to an aerosol of leukotriene D4. In a second series of experiments, intravenous CDP-840 (5 mg/kg; 30 min before challenge) showed improved potency, producing 82% inhibition of the early and 51% inhibition of the late phase response. CDP-840 was inactive when tested intravenously at 1 mg/kg and was inactive against the 3-5 h response when administered after the early phase response (5 mg/kg; i.v. 60 min post antigen challenge). The novel phosphodiesterase IV inhibitor CDP-840 selectively inhibited antigen-induced bronchoconstriction in conscious squirrel monkeys. This effect appears to be independent of any direct bronchodil...Continue Reading

Citations

Jul 5, 2005·Expert Opinion on Investigational Drugs·H J Dyke, J G Montana
Feb 7, 2001·Biochemical Pharmacology·W S Wong, D S Koh
May 30, 2008·Journal of Clinical Pharmacology·Kathleen A NevilleGregory L Kearns
Jun 19, 2004·Toxicologic Pathology·Patricia E LoscoFrancis M Cuss
May 18, 2006·Journal of Mass Spectrometry : JMS·Kevin P BatemanDeborah Nicoll-Griffith

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