Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative

The effects of the novel veterinary sedative, medetomidine, were studied in rats. In addition to a dose-dependent sedation, which at high doses (greater than 100 micrograms/kg) included loss of the righting reflex and hypothermia, there was a concurrent decrease in the turnover rate of biogenic amines in the brain. Noradrenaline turnover was dose dependently decreased as judged by (i) the decrease in the brain concentration of its metabolite, MHPG-SO4, (ii) a decrease in the ability of alpha-methyl-p-tyrosine methyl ester to deplete brain noradrenaline stores and (iii) a dose-dependent decrease in the level of unconjugated MHPG in the CSF of freely moving rats. Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine. Serotonin turnover as estimated by the ratio of biogenic amine to its metabolite was also significantly depressed. These changes in brain biogenic amine turnover were inhibited by prior or simultaneous administration of alpha 2-adrenoceptor antagonists, either yohimbine or the more specific, novel alpha 2-antagonist, atipamezole.