Affinity of detomidine, medetomidine and xylazine for alpha‐2 adrenergic receptor subtypes

Abstract

alpha 2-Adrenergic receptor agonists are widely used in veterinary medicine as sedative/hypnotic agents. Four pharmacological subtypes of the alpha 2-adrenergic receptor (A, B, C and D) have been identified based primarily on differences in affinity for several drugs. The purpose of this study was to examine the affinities of the sedative agents, xylazine, detomidine and medetomidine at the four alpha 2-adrenergic receptor subtypes. Saturation and inhibition binding curves were performed in membranes of tissues containing only one subtype of alpha 2-adrenergic receptor. The KD for the alpha 2-adrenergic receptor radioligand, [3H]-MK-912, in HT29 cells (alpha 2A-), neonatal rat lung (alpha 2B-), OK cells (alpha 2C-) and PC12 cells transfected with RG20 (alpha 2D-) were 0.38 +/- 0.08 nM, 0.70 +/- 0.5 nM. 0.07 +/- 0.02 nM and 0.87 +/- 0.03 nM, respectively. Detomidine and medetomidine had approximately a 100 fold higher affinity for all the alpha 2-adrenergic receptors compared to xylazine but neither agonist displayed selectivity for the alpha 2-adrenergic receptor subtypes. These data suggest that available sedative/hypnotic alpha 2-adrenergic receptor agonists can not discriminate between the four known alpha 2-adrenergic receptor subtypes.

Antagonistic Effects of Atipamezole and Yohimbine on Xylazine-Induced Diuresis in Healthy Dogs

“…Atipamezole produces stronger and relatively longer hypertension [4,8,20]. Moreover, the  2 -adrenoceptor selectivity of yohimbine is 100-fold lower for  2D subtypes compared with that of atipamezole, and yohimbine has no imidazoline receptor affinity [4,8,14,20]. Therefore, we suggest that yohimbine does not stimulate ANP release.…”

“…The  2 /  1 receptor binding selectivity of xylazine is 160, whereas those of medetomidine, detomidine and clonidine are 1620, 260 and 220, respectively [14]. Xylazine is less lipophilic than medetomidine, detomidine and clonidine [14].…”

“…71 (5): [539][540][541][542][543][544][545][546][547][548] 2009 Xylazine (2(2,6 dimethylphenylamino)-5,6-dihydro-4H-1,3 thiazine hydrochloride) is a potent  2 -adrenoceptor agonist, clonidine analogue and non-narcotic drug [5]. The  2 /  1 receptor binding selectivity of xylazine is 160, whereas those of medetomidine, detomidine and clonidine are 1620, 260 and 220, respectively [14]. Xylazine is less lipophilic than medetomidine, detomidine and clonidine [14].…”

“…The  2 /  1 receptor binding selectivity of xylazine is 160, whereas those of medetomidine, detomidine and clonidine are 1620, 260 and 220, respectively [14]. Xylazine is less lipophilic than medetomidine, detomidine and clonidine [14]. It acts on presynaptic and postsynaptic receptors of the central and peripheral nervous systems as an  2 -adrenoceptor agonist and inhibits the effects of postganglionic nerve stimulation.…”

Topical Mydriatics Affect Light-Evoked Retinal Responses in Anesthetized Mice

“…Of the different anesthetics used, a combination of, ketamine, an NMDA receptor antagonist 5 and xylazine 6, an α2-receptor agonist are used for a variety of species. Electroretinograms (ERGs) from mice are routinely recorded using combinations of atropine and phyenylephrine for mydriasis, and, ketamine and xylazine for anesthesia (for review see, 7, 8.…”