title: Adenosine A1 receptor antagonist versus montelukast on airway reactivity and inflammation.
abstract: Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating adenosine A(1) receptors. Previously, it is reported that a high dose of L-97-1, a water-soluble, small molecule adenosine A(1) receptor antagonist, blocks early and late allergic responses, and bronchial hyper-responsiveness to histamine in a hyper-responsive rabbit model of allergic asthma. Effects of a lower dose of L-97-1 are compared to montelukast, a cysteinyl leukotriene-1 receptor antagonist on early allergic response, late allergic response, bronchial hyper-responsiveness, and inflammatory cells in bronchoalveolar lavage (BAL) fluid following house dust mite administration. Rabbits received intraperitoneal injections of house dust mite extract within 24 h of birth followed by booster house dust mite injections. Hyper-responsive rabbits received aerosolized house dust mite (2500 allergen units), 1 h after intragastric administration of L-97-1 (1 mg/kg) or montelukast (0.15 mg/kg) and lung dynamic compliance was measured for 6 h. Lung dynamic compliance was significantly higher following L-97-1 at all time points and with montelukast at 60-300 min following house dust mite (P<0.05). L-97-1 blocks both early and late allergic responses. Montelukast blocks only the late allergic response. Both L-97-1 and montelukast significantly blocked bronchial hyper-responsiveness at 24 h (P<0.05). Both L-97-1 and montelukast significantly reduced BAL eosinophils at 6 h and neutrophils at 6 and 24 h (P<0.05). L-97-1 significantly reduced BAL lymphocytes at 6 and 24 h (P<0.05). Montelukast significantly reduced BAL macrophages at 6 and 24 h (P<0.05). By blocking both bronchoconstriction and airway inflammation, L-97-1 may be an effective oral anti-asthma treatment.
authors.affiliation: Department of Pharmacology, East Carolina University, Greenville, NC, United States.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nadeem
authors.forename: Peter C M
authors.initials: PC
authors.lastname: Obiefuna
authors.forename: Constance N
authors.initials: CN
authors.lastname: Wilson
authors.forename: S Jamal
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003521:Cyclopropanes; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects; D006632:Histamine; D007249:Inflammation / Q000517:prevention & control; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008170:Lung Compliance / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D011687:Purines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D039981:Pyroglyphidae / Q000276:immunology; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D013440:Sulfides; D013997:Time Factors
chemical_list: C505457:3-(2-(4-aminophenyl)ethyl)-8-benzyl-7-(2-ethyl(2-hydroxyethyl)aminoethyl)-1-propyl-3,7-dihydropurine-2,6-dione; D000085:Acetates; D058916:Adenosine A1 Receptor Antagonists; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011687:Purines; D011804:Quinolines; D013440:Sulfides; D006632:Histamine; C093875:montelukast