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Effect of the α2-receptor agonists medetomidine, detomidine, xylazine, and romifidine on the ketamine metabolism in equines assessed with enantioselective capillary electrophoresis


Sandbaumhüter, Friederike A; Theurillat, Regula; Bettschart-Wolfensberger, Regula; Thormann, Wolfgang (2017). Effect of the α2-receptor agonists medetomidine, detomidine, xylazine, and romifidine on the ketamine metabolism in equines assessed with enantioselective capillary electrophoresis. Electrophoresis, 38(15):1895-1904.

Abstract

The combination of ketamine and an α2 -receptor agonist is often used in veterinary medicine. Four different α2 -receptor agonists, medetomidine, detomidine, xylazine, and romifidine, which differ in their chemical structure and thus in selectivity for the α2 -receptor and in the sedative and analgesic potency, are typically employed during surgery of equines. Recovery following anesthesia with ketamine and an α2 -receptor agonist is dependent on the α2 -receptor agonist. This prompted us to investigate (i) the inhibition characteristics for the N-demethylation of ketamine to norketamine and (ii) the formation of the ketamine metabolites norketamine, 6-hydroxynorketamine (6HNK), and 5,6-dehydronorketamine (DHNK) in presence of the four α2 -receptor agonists and equine liver microsomes. Samples were analyzed with enantioselective capillary electrophoresis using highly sulfated γ-cyclodextrin as chiral selector. All four α2 -receptor agonists have an impact on the ketamine metabolism. Medetomidine was found to be the strongest inhibitor, followed by detomidine, whereas xylazine and romifidine showed almost no effect on the ketamine N-demethylation in the inhibition studies with a short-incubation period of the reaction mixture. After prolonged incubation, inhibition with xylazine and romifidine was also observed. The formation of 6HNK and DHNK is affected by all selected α2 -receptor agonists. With medetomidine, levels of these metabolites are reduced compared to the case without an α2 -receptor agonist. For detomidine, xylazine, and romifidine, the opposite was found.

Abstract

The combination of ketamine and an α2 -receptor agonist is often used in veterinary medicine. Four different α2 -receptor agonists, medetomidine, detomidine, xylazine, and romifidine, which differ in their chemical structure and thus in selectivity for the α2 -receptor and in the sedative and analgesic potency, are typically employed during surgery of equines. Recovery following anesthesia with ketamine and an α2 -receptor agonist is dependent on the α2 -receptor agonist. This prompted us to investigate (i) the inhibition characteristics for the N-demethylation of ketamine to norketamine and (ii) the formation of the ketamine metabolites norketamine, 6-hydroxynorketamine (6HNK), and 5,6-dehydronorketamine (DHNK) in presence of the four α2 -receptor agonists and equine liver microsomes. Samples were analyzed with enantioselective capillary electrophoresis using highly sulfated γ-cyclodextrin as chiral selector. All four α2 -receptor agonists have an impact on the ketamine metabolism. Medetomidine was found to be the strongest inhibitor, followed by detomidine, whereas xylazine and romifidine showed almost no effect on the ketamine N-demethylation in the inhibition studies with a short-incubation period of the reaction mixture. After prolonged incubation, inhibition with xylazine and romifidine was also observed. The formation of 6HNK and DHNK is affected by all selected α2 -receptor agonists. With medetomidine, levels of these metabolites are reduced compared to the case without an α2 -receptor agonist. For detomidine, xylazine, and romifidine, the opposite was found.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Equine Department
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Uncontrolled Keywords:Capillary electrophoresis; Equine liver microsomes; Ketamine; α2-receptor agonist
Language:English
Date:2017
Deposited On:29 Jun 2017 08:52
Last Modified:04 Aug 2017 03:39
Publisher:Wiley-VCH Verlag
ISSN:0173-0835
Publisher DOI:https://doi.org/10.1002/elps.201700017
PubMed ID:28251651

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