AFFINITY OF DETOMIDINE, MEDETOMIDINE AND XYLAZINE FOR ALPHA-2-ADRENERGIC RECEPTOR SUBTYPES

alpha(2)-Adrenergic receptor agonists are widely used in veterinary me dicine as sedative/hypnotic agents. Pour pharmacological subtypes of t he alpha(2)-adrenergic receptor (A, B, C and D) have been identified b ased primarily on differences in affinity for several drugs. The purpo se 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 perf ormed in membranes of tissues containing only one subtype of a(2)-adre nergic receptor. The K-D for the alpha(2)-adrenergic receptor radiolig and, [H-3]-MK-912, in HT29 cells (alpha(2A-)), neonatal rat lung (alph a(2B-)), OK cells (alpha(2C-)) and PC12 cells transfected with RG20 (a lpha(2D-)) were 0.38 +/- 0.08 nM, 0.70 +/- 0.5 nM, 0.07 +/- 0.02 nM an d 0.87 +/- 0.03 nM, respectively. Detomidine and medetomidine had appr oximately a 100 fold higher affinity for all the alpha(2)-adrenergic r eceptors compared to xylazine but neither agonist displayed selectivit y for the alpha(2)-adrenergic receptor subtypes. These data suggest th at available sedative/ hypnotic alpha(2)-adrenergic receptor agonists can not discriminate between the four known alpha(2)-adrenergic recept or subtypes.