title: Methoctramine, a cardioselective muscarinic cholinergic antagonist, prevents fentanyl-induced bradycardia in the dog.
abstract: A controlled study examining the effects of the cardioselective muscarinic cholinergic antagonist methoctramine on fentanyl-induced bradycardia was performed in six dogs. Five doses of methoctramine (6, 10, 20, 30 and 60 micrograms/kg) followed by fentanyl (20 micrograms/kg) were administered randomly on separate days. Fentanyl caused a significant reduction in heart rate from baseline values. Moreover, fentanyl produced a variety of arrhythmogenic actions indicative of vagal hyperactivity, including sinus bradycardia, second-degree atrioventricular block and ventricular and supraventricular escape beats. Administration of methoctramine 5 min before fentanyl injection prevented the bradycardic effects of fentanyl in a dose-dependent manner, with high doses of methoctramine causing sinus tachycardia. Using regression analysis, the dose of methoctramine necessary to prevent fentanyl-induced bradyarrhythmias without causing tachycardia was calculated as 14.4 micrograms/kg. The study confirmed that fentanyl administration in the conscious dog causes profound bradycardia with bradyarrhythmias. The cardioselective muscarinic antagonist agent methoctramine prevented the bradycardic effects of fentanyl.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul 55108, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Hendrix
authors.forename: E P
authors.initials: EP
authors.lastname: Robinson
authors.forename: M R
authors.initials: MR
authors.lastname: Raffe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000517:prevention & control* / Q000662:veterinary; D002405:Catheterization, Central Venous; D002452:Cell Count / Q000187:drug effects; D003959:Diamines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005283:Fentanyl / Q000008:administration & dosage / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012044:Regression Analysis; D013610:Tachycardia / Q000188:drug therapy / Q000662:veterinary
chemical_list: D003959:Diamines; D010276:Parasympatholytics; C054938:methoctramine; D005283:Fentanyl