PT - JOURNAL ARTICLE AU - Milenko Cicmil AU - Stephen Marshall AU - Marilyn Mather AU - Ken McKechnie TI - A novel dual-agonist challenge model in guinea pigs for assessment of individual and combined muscarinics antagonists and b<sub>2</sub> adrenoceptor agonists bronchodilator efficacy DP - 2011 Sep 01 TA - European Respiratory Journal PG - p1785 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p1785.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p1785.full SO - Eur Respir J2011 Sep 01; 38 AB - The guinea pig broncoconstriction model has been shown to be predictive for both muscarinics receptor antagonist and b2-adrenoceptor agonist efficacy in humans. Here we describe a novel in vivo model of bronchoconstriction in guinea pigs, stimulated by two different agonists, histamine and methacholine. This dual-agonist challenge model can be used to assess the potency of both M3 antagonists and b2-adrenoceptor agonists individually and in combination. This can be extended to investigate compounds with dual activity: Muscarinic receptor antagonists and β2-adrenoceptor agonists (MABA).Following administration of test compounds three separate bronchoconstrictor challenges were given to each animal:The β2 potency was assessed after challenging guinea pigs with histamine.Methacholine challenge in the same animal allowed assessment of combined in vivo potency at both β2 and M3 receptors.Finally, the potency of the compounds at M3 receptor alone was assessed using methacholine challenge in the presence of propranolol.No significant difference in between single- and dual-challenge model was observed for the both M3 antagonists and b2-adrenoceptor agonists tested with regards to in vivo potency or duration of action, therefore validating our approach. In addition to reducing number of animals used, this approach allowed us to assess individual and combined potency and duration of action for both M3 antagonists and b2-adrenoceptor agonists in single animal. This novel bronchoconstriction model provides a robust mechanism for the future testing of MABA compounds.