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Effect of the α 2 ‐receptor agonists medetomidine, detomidine, xylazine, and romifidine on the ketamine metabolism in equines assessed with enantioselective capillary electrophoresis
Author(s) -
Sandbaumhüter Friederike A.,
Theurillat Regula,
BettschartWolfensberger Regula,
Thormann Wolfgang
Publication year - 2017
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201700017
Subject(s) - medetomidine , xylazine , chemistry , detomidine , ketamine , agonist , pharmacology , receptor , medicine , anesthesia , biochemistry , heart rate , blood pressure
The combination of ketamine and an α 2 ‐receptor agonist is often used in veterinary medicine. Four different α 2 ‐receptor agonists, medetomidine, detomidine, xylazine, and romifidine, which differ in their chemical structure and thus in selectivity for the α 2 ‐receptor and in the sedative and analgesic potency, are typically employed during surgery of equines. Recovery following anesthesia with ketamine and an α 2 ‐receptor agonist is dependent on the α 2 ‐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 α 2 ‐receptor agonists and equine liver microsomes. Samples were analyzed with enantioselective capillary electrophoresis using highly sulfated γ‐cyclodextrin as chiral selector. All four α 2 ‐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 α 2 ‐receptor agonists. With medetomidine, levels of these metabolites are reduced compared to the case without an α 2 ‐receptor agonist. For detomidine, xylazine, and romifidine, the opposite was found.