The commonly used sedative α₂-adrenoceptor agonist
dexmedetomidine has adverse cardiovascular effects in dogs that can be
prevented by concomitant administration of the peripherally acting α₂-adrenoceptor
antagonist MK-467. An ancillary effect of dexmedetomidine is to
decrease insulin release from the pancreas, whereas MK-467 stimulates
insulin release. This study assessed the effects of co-administered
dexmedetomidine and MK-467 in a canine glibenclamide-induced
hypoglycaemia model. In a randomised, cross-over experiment, eight
beagle dogs received five intravenous treatments, comprising two
administrations of saline, with dexmedetomidine or dexmedetomidine and
MK-467, and three administrations of glibenclamide, with saline,
dexmedetomidine or dexmedetomidine and MK-467. Plasma concentrations of
glucose, lactate, insulin, glucagon and the test drugs were monitored.
Administration of glibenclamide significantly increased insulin
secretion and decreased blood glucose concentrations. Dexmedetomidine
counteracted glibenclamide-evoked hypoglycaemia. This was opposed by the
α₂-adrenoceptor antagonist MK-467, but the
glibenclamide-evoked hypoglycaemia was not potentiated by
co-administration of dexmedetomidine and MK-467. None of the dogs
developed uncontrolled hypoglycaemia. Thus, the combination of
dexmedetomidine and MK-467 appeared to be safe in this canine
hypoglycaemia model. Nevertheless, when MK-467 is used to alleviate the
undesired cardiovascular effects of α₂-adrenoceptor agonists
in dogs, it should be used with caution in animals at risk for
hypoglycaemia because of its insulin-releasing and hypoglycaemic
effects.