The effect of MK-467, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia after intravenous administration in conscious cats

Juhana Honkavaara, Bruno H Pypendop, Heta Turunen, Jan Ilkiw

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective To determine a dose of MK-467, a peripheral α2-adrenoceptor antagonist, which, when administered intravenously (IV) concomitantly with 25 μg kg−1 of dexmedetomidine, will prevent bradycardia without altering sedation in cats. Study design Prospective, randomized, controlled, blinded, experimental, crossover study. Animals Eight healthy, adult, purpose-bred cats. Methods 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−1 of 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. Results 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. Conclusions and clinical relevance 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.

Original languageEnglish (US)
Pages (from-to)42-51
Number of pages10
JournalVeterinary Anaesthesia and Analgesia
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

L 659066
dexmedetomidine
Dexmedetomidine
adrenergic receptors
sedation
Bradycardia
intravenous injection
Intravenous Administration
Adrenergic Receptors
antagonists
Cats
cats
heart rate
Heart Rate
Therapeutics
Telemetry
sedatives
renal failure
telemetry
dosage

Keywords

  • cat
  • dexmedetomidine
  • heart rate
  • MK-467
  • sedation

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{59f6135671e94e869478eafa7af61627,
title = "The effect of MK-467, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia after intravenous administration in conscious cats",
abstract = "Objective To determine a dose of MK-467, a peripheral α2-adrenoceptor antagonist, which, when administered intravenously (IV) concomitantly with 25 μg kg−1 of dexmedetomidine, will prevent bradycardia without altering sedation in cats. Study design Prospective, randomized, controlled, blinded, experimental, crossover study. Animals Eight healthy, adult, purpose-bred cats. Methods 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−1 of 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. Results 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. Conclusions and clinical relevance 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.",
keywords = "cat, dexmedetomidine, heart rate, MK-467, sedation",
author = "Juhana Honkavaara and Pypendop, {Bruno H} and Heta Turunen and Jan Ilkiw",
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T1 - The effect of MK-467, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia after intravenous administration in conscious cats

AU - Honkavaara, Juhana

AU - Pypendop, Bruno H

AU - Turunen, Heta

AU - Ilkiw, Jan

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Objective To determine a dose of MK-467, a peripheral α2-adrenoceptor antagonist, which, when administered intravenously (IV) concomitantly with 25 μg kg−1 of dexmedetomidine, will prevent bradycardia without altering sedation in cats. Study design Prospective, randomized, controlled, blinded, experimental, crossover study. Animals Eight healthy, adult, purpose-bred cats. Methods 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−1 of 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. Results 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. Conclusions and clinical relevance 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.

AB - Objective To determine a dose of MK-467, a peripheral α2-adrenoceptor antagonist, which, when administered intravenously (IV) concomitantly with 25 μg kg−1 of dexmedetomidine, will prevent bradycardia without altering sedation in cats. Study design Prospective, randomized, controlled, blinded, experimental, crossover study. Animals Eight healthy, adult, purpose-bred cats. Methods 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−1 of 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. Results 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. Conclusions and clinical relevance 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.

KW - cat

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KW - sedation

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