title: The effect of MK-467, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia after intravenous administration in conscious cats.
abstract: To determine a dose of MK-467, a peripheral α2-adrenoceptor antagonist, which, when administered intravenously (IV) concomitantly with 25 μg kg-1of dexmedetomidine, will prevent bradycardia without altering sedation in cats.
  
  
  
  Prospective, randomized, controlled, blinded, experimental, crossover study.
  
  
  
  Eight healthy, adult, purpose-bred cats.
  
  
  
  Cats were administered seven IV treatments were administered at least 2 weeks apart, consisting of dexmedetomidine 12.5 μg kg-1(D12.5) and 25 μg kg-1(D25), MK-467 300 μg kg-1(M300), and D25 combined with 75, 150, 300 and 600 μg kg-1of MK-467 (D25M 75, D25M150, D25M300 and D25M600, respectively). Heart rates (HR) were recorded via telemetry and sedation assessed with a simple descriptive score and a visual analogue scale prior to treatments and at intervals until 8 hours thereafter.
  
  
  
  Data from one cat were excluded because it developed renal failure. Heart rate decreased significantly from baseline after all treatments except M300 and D25M600. The lowest HR for each treatment with dexmedetomidine were 99 ± 21 (D25), 103 ± 22 (D12.5), 114 ± 10 (D25M75), 117 ± 17 (D25M150), 121 ± 12 (D25M300) and 139 ± 15 (D25M600) beats minute-1. Sedation increased with all treatments that included dexmedetomidine, whereas M300 did not induce any central effects. In comparison with D25, the combination of MK-467 with dexmedetomidine reduced the duration of detectable sedation.
  
  
  
  MK-467 dose-dependently attenuated the bradycardia associated with dexmedetomidine, and shortened the sedative effect without altering its quality. MK-467 may be useful in attenuating reductions in HR in conscious cats administered dexmedetomidine.
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. Electronic address: jussi.honkavaara@helsinki.fi.
authors.forename: Juhana
authors.initials: J
authors.lastname: Honkavaara
authors.affiliation: Department of Radiological and Surgical Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pypendop
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Heta
authors.initials: H
authors.lastname: Turunen
authors.affiliation: Department of Radiological and Surgical Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Ilkiw
keywords: MK-467; cat; dexmedetomidine; heart rate; sedation