Effect of detomidine on the release and turnover of noradrenaline in rat brain.

The effect of detomidine, a novel veterinary sedative/analgesic, on the release and turnover of noradrenaline in rat brain was studied using both in vitro and in vivo techniques. Xylazine was included in the studies for comparison. Rat occipital cortex slices were preloaded with 3H-noradrenaline and the potassium-evoked release of tritium was measured using a superfusion system. Both detomidine and xylazine produced concentration dependent inhibition of stimulation evoked tritium release. A maximal inhibition of 66 and 50% was achieved at detomidine and xylazine concentrations of 1 X 10(-7) and 1 X 10(-6) M, respectively. The dose-response curve of detomidine was shifted to the right in a parallel manner by the selective alpha 2-antagonist idazoxan. Detomidine, while not altering the endogenous levels of noradrenaline, dopamine and 5-hydroxytryptamine, induced a dose-dependent inhibition of noradrenaline turnover as measured by the alpha-methyl-p-tyrosine method. Moreover, detomidine decreased the concentration of MHPG-SO4, the principal metabolite of central noradrenaline, in rat brain. Xylazine was in these tests at least two orders of magnitude less potent than detomidine.