Effects of MK-467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs

Journal of Veterinary Pharmacology and Therapeutics
R C BennettOuti M Vainio

Abstract

We investigated the influence of the peripherally acting α2 -adrenoceptor antagonist MK-467 on the sedative and antinociceptive actions and plasma drug concentrations of medetomidine, an α2 -adrenoceptor agonist that is used in veterinary medicine as a sedative and analgesic agent. Eight healthy beagle dogs received intravenous medetomidine (10 μg/kg) or medetomidine with MK-467 (250 μg/kg) in a randomized crossover design. A standardized nociceptive pressure stimulus was applied to a nail bed of a hindlimb. Times for withdrawal of the limb and for head lift were measured, and sedation was scored. EEG data were collected prior to and after stimulation. Plasma drug concentrations were measured. Co-administration of MK-467 significantly attenuated medetomidine analgesia, as assessed with limb withdrawal, and also shortened the duration of sedation. The apparent plasma clearance of both enantiomers of medetomidine, dexmedetomidine and levomedetomidine, was more than doubled in the presence of MK-467. Antagonism by MK-467 of medetomidine-evoked vasoconstriction is seen as the mechanism behind this pharmacokinetic drug interaction. Thus, MK-467 attenuated the antinociceptive and sedative effects of medetomidine. This can probably be...Continue Reading

References

Jun 1, 1989·Journal of Veterinary Pharmacology and Therapeutics·O VainioL Palmu
Dec 1, 1986·Journal of Autonomic Pharmacology·J M SavolaN T Kärki
Oct 1, 1995·Journal of Veterinary Pharmacology and Therapeutics·S SalonenM Anttila
Dec 5, 1998·Research in Veterinary Science·C E BryantK W Clarke
Dec 9, 1998·Veterinary Surgery : VS·B H Pypendop, J P Verstegen
Mar 29, 2000·Journal of Pharmaceutical Sciences·S DuttaT Ebert
Apr 4, 2000·Journal of Veterinary Pharmacology and Therapeutics·E KuuselaO Vainio
Feb 21, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sanna KaivosaariJyrki Taskinen
May 16, 2008·Biometrical Journal. Biometrische Zeitschrift·Torsten HothornPeter Westfall
Aug 13, 2011·Veterinary Anaesthesia and Analgesia·Flavia RestituttiOuti M Vainio
Nov 25, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Juhana HonkavaaraMika Scheinin

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Citations

Apr 2, 2020·American Journal of Veterinary Research·Vilhelmiina HuuskonenOuti M Vainio
Jul 28, 2020·Animals : an Open Access Journal From MDPI·Joëlle SiegenthalerOlivier Louis Levionnois

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