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 co mpared to those of the nonselective competitive muscarinic antagonist, atropine. Methoctramine or atropine, 6, 10, 30, 60 mu g/kg, or steril e isotonic saline, was administered intravenously to six conscious dog s in cross-over studies, Methoctramine administration caused dose-depe ndent tachycardia without affecting intestinal motility, while atropin e administration caused dose-dependent tachycardia accompanied by sign ificant reductions in small intestinal motility, Additionally, methoct ramine did not inhibit intestinal smooth muscle contractile activity i nitiated by the muscarinic agonist bethanechol, while atropine inhibit ed 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 mu g/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 veterin ary patients in which nonselective muscarinic antagonists have the pot ential to produce untoward effects on intestinal motility.