Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist

Abstract

Medetomidine (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole) was tested for α 2-adrenoceptor agonist activity and compared to several reference agents. In binding studies carried out with rat brain membrane preparations, medetomidine showed high affinity for α 2-adrenoceptors, as measured by the displacement of [ 3H]clonidine (K i 1.08 nM compared to 1.62, 3.20, 6.22 and 194 nM for detomidine, clonidine, UK 14,304 and xylazine, respectively). The affinity of medetomidine for α 1-adrenoceptors, as measured by [ 3H]prazosin displacement, was much weaker, yielding a relative α 2/ α 1 selectivity ratio of 1620 which is 5–10 times higher than that of the reference compounds. Medetomidine caused a concentration-dependent inhibition of the twitch response in electrically stimulated mouse vas deferens with a pD 2 value of 9.0 compared to that of 8.6, 8.5, 8.2 and 7.1 for detomidine, clonidine, UK 14,304 and xylazine, respectively. The effect of medetomidine was antagonized by idazoxan. In anaesthetized rats, medetomidine caused a dose-dependent mydriasis which could be reversed by α 2-adrenoceptor blockade. In receptor binding experiments and isolated organs medetomidine had no affinity or effects of β 1-, β 2-, H 1, H 2, 5-HT 1, 5-HT 2, muscarine, dopamine, tryptamine, GABA, opiate and benzodiazepine receptors. Based on these results, medetomidine can be classified as a potent, selective and specific α 2-adrenoceptor agonist.