Virtanen R, MacDonald E, Kaisila M
Acta Pharmacol Toxicol (Copenh). 1986 May;58(5):348-54. doi: 10.1111/j.1600-0773.1986.tb00120.x.
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.
采用体外和体内技术，研究了新型兽用镇静/镇痛药地托咪定对大鼠脑内去甲肾上腺素释放和周转的影响。研究中纳入赛拉嗪作为对照。用3H-去甲肾上腺素预加载大鼠枕叶皮质切片，并使用灌流系统测量钾诱发的氚释放。地托咪定和赛拉嗪均产生浓度依赖性的刺激诱发氚释放抑制作用。地托咪定和赛拉嗪浓度分别为1×10（-7）和1×10（-6）M时，最大抑制率分别为66%和50%。选择性α2拮抗剂咪唑克生使地托咪定的剂量-反应曲线平行右移。地托咪定虽然不改变去甲肾上腺素、多巴胺和5-羟色胺的内源性水平，但通过α-甲基-p-酪氨酸法测量，它可诱导剂量依赖性的去甲肾上腺素周转抑制。此外，地托咪定降低了大鼠脑中去甲肾上腺素的主要代谢产物MHPG-SO4的浓度。在这些试验中，赛拉嗪的效力比地托咪定至少低两个数量级。
