Effects of a selective phosphodiesterase IV inhibitor (CDP-840) in a leukotriene-dependent non-human primate model of allergic asthma
| Autor: | H. Piechuta, Dwight Macdonald, Ian W. Rodger, C. S. Mcfarlane, M. McAuliffe, Thomas R. Jones |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Pharmacology
Leukotriene medicine.medical_specialty Allergy Leukotriene D4 biology Physiology medicine.drug_class General Medicine medicine.disease chemistry.chemical_compound Endocrinology chemistry Antigen Enzyme inhibitor Physiology (medical) Bronchodilator Internal medicine medicine biology.protein Potency Bronchoconstriction medicine.symptom |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 76:210-217 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y98-030 |
| Popis: | 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.Key words: selective phosphodiesterase IV inhibitor, CDP-840, antigen-induced bronchoconstriction, non-human primate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|