Effects of a selective and a nonselective muscarinic cholinergic antagonist on heart rate and intestinal motility in dogs.
The effects of methoctramine, a cardioselective muscarinic cholinergic antagonist, on heart rate and small intestinal motor activity were compared to those of the nonselective competitive muscarinic antagonist, atropine. Methoctramine or atropine, 6, 10, 30, 60 micrograms/kg, or sterile isotonic saline, was administered intravenously to six conscious dogs in cross-over studies. Methoctramine administration caused dose-dependent tachycardia without affecting intestinal motility, while atropine administration caused dose-dependent tachycardia accompanied by significant reductions in small intestinal motility. Additionally, methoctramine did not inhibit intestinal smooth muscle contractile activity initiated by the muscarinic agonist bethanechol, while atropine inhibited bethanechol-induced contractile activity in a dose-dependent manner. Calculated, dosages of methoctramine and atropine required to produce a 50% increase in heart rate over baseline were 35.1 +/- 5.3 and 39.5 +/- 6.2 micrograms/kg, respectively. This dosage of atropine caused a 93 +/- 13.9% reduction in intestinal motility. These findings suggest that selective muscarinic antagonists may be useful drugs for those veterinary patients in which nonselective muscarinic antagonists have the potential to produce untoward effects on intestinal motility.
Hendrix
P K
PK
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul 55108, USA. hendr009@maroon.tc.umn.edu
Robinson
E P
EP
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D003959:Diamines / Q000009:adverse effects / Q000494:pharmacology*; D004283:Dog Diseases / Q000139:chemically induced; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000009:adverse effects / Q000494:pharmacology*; D012044:Regression Analysis; D013610:Tachycardia / Q000662:veterinary
D003959:Diamines; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D001285:Atropine; C054938:methoctramine