title: Bronchodilator activity of the selective muscarinic antagonist revatropate in horses with heaves.
abstract: Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential advantages over non-specific antimuscarinic agents such as ipratropium. Protocol 1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded, negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and 2mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid (within 1h) and significant improvement in airway function. The highest doses of both drugs had no significant effect on gastrointestinal sound score or iris function, but resulted in tacky mucous membranes and reduced gastrointestinal sound score in some horses. In Protocol 2, a cross-over design comparing the duration of action of inhaled revatropate (1mg), ipratropium (0.3mg) and saline, some indices of airway function were improved for between 5 and 6h after revatropate administration, and for between 6 and 24h after ipratropium administration. Inhaled revatropate and ipratropium had similar effects on airway function, with no significant difference between their efficacies. Importantly, however, only revatropate significantly improved clinical scores of breathing effort, improving combined clinical score at the 1h time point and abdominal score at the 1-3h time points. No significant adverse events were observed in Protocol 2, although some horses had reduced gastrointestinal sound scores. Inhaled revatropate is therefore a safe and effective bronchodilator for treating airway obstruction in heaves.
authors: Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, Midlothian EH25 9RG, UK. bruce.mcgorum@ed.ac.uk
authors: B C
authors: BC
authors: McGorum
authors: D R
authors: DR
authors: Nicholas
authors: A P
authors: AP
authors: Foster
authors: D J
authors: DJ
authors: Shaw
authors: R S
authors: RS
authors: Pirie
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D009241:Ipratropium / Q000009:adverse effects / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000662:veterinary*; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D011812:Quinuclidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D011812:Quinuclidines; C105222:revatropate; D009241:Ipratropium