Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes.
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.
Schwartz
D D
DD
Department of Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Alabama 36849, USA.
Clark
T P
TP
D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D019073:HT29 Cells; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D020926:Medetomidine; D016716:PC12 Cells; D011807:Quinolizines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014991:Xylazine / Q000494:pharmacology*
D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011807:Quinolizines; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; D014991:Xylazine; C041255:detomidine; D020926:Medetomidine