Bronchodilator activity of the selective muscarinic antagonist revatropate in horses with heaves |
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| Authors: | B.C. McGorum D.R. Nicholas A.P. Foster D.J. Shaw R.S. Pirie |
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| Affiliation: | 1. Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, Midlothian EH25 9RG, UK;2. Veterinary Medicine Discovery, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK;1. University of Melbourne Equine Centre, 250 Princes Highway, Werribee, Victoria 3030, Australia;2. Faculty of Veterinary Science, University of Melbourne, 250 Princes Highway, Werribee, Victoria 3030, Australia;1. Faculty of Science and Technology, Department of Mathematics and Natural Science, University of Stavanger, N-4036 Stavanger, Norway;2. Department of Green Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt;1. Institute for Heart and Lung Health, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;2. Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Institute, University of British Columbia, Vancouver, British Columbia, Canada;3. Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada;4. Centre for Health Evaluation and Outcome Sciences, University of British Columbia, Vancouver, British Columbia, Canada;5. Pharmacy Department, Grenoble University Hospital, Grenoble, France;1. Philip Leverhulme Equine Hospital, Leahurst Campus, School of Veterinary Sciences, University of Liverpool, Neston, Wirral CH64 7TE, UK;2. Department of Epidemiology and Public Health, Institute of Infection and Global Health, Leahurst Campus, University of Liverpool, Neston, Wirral CH64 7TE, UK;3. Cotts Farm Equine Hospital, Narberth, Pembrokeshire SA67 8EY, UK;4. Department of Clinical Veterinary Medicine, University of Bristol, Langford, Somerset BS40 5DU, UK;5. Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Leahurst Campus, University of Liverpool, Neston, Wirral CH64 7TE, UK |
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| Abstract: | Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M3 and M1) 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 2 mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid (within 1 h) 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 (1 mg), ipratropium (0.3 mg) and saline, some indices of airway function were improved for between 5 and 6 h after revatropate administration, and for between 6 and 24 h 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 1 h time point and abdominal score at the 1–3 h 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. |
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