Effects of a selective phosphodiesterase IV inhibitor (CDP-840) in a leukotriene-dependent non-human primate model of allergic asthma.
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| 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 bronchodilator action. It is concluded that the activity of CDP-840 in this model may be due to an inhibitory effect on mediator (e.g., leukotriene) release.
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| Authors | T R Jones, M McAuliffe, C S McFarlane, H Piechuta, D Macdonald, I W Rodger |
| Journal | Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 76 Issue 2 Pg. 210-7 (Feb 1998) ISSN: 0008-4212 [Print] Canada |
| PMID | 9635162 (Publication Type: Journal Article) |
| Chemical References |
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