Virtanen R, Ruskoaho H, Nyman L
J Vet Pharmacol Ther. 1985 Mar;8(1):30-7. doi: 10.1111/j.1365-2885.1985.tb00921.x.
The sedative effect and mechanism of action of a novel imidazole derivative, detomidine, were studied in laboratory animals. Three methods were used to quantify drug-induced sedation: (i) decrease in spontaneous activity of mice; (ii) increase in barbiturate induced anaesthesia time in mice; (iii) loss of righting reflex in chicks. Clonidine and xylazine were included in the studies for comparison. The sedative potency of detomidine was shown to be approximately equal to that of clonidine and much higher than that of xylazine. In all tests, the sedative effect of detomidine was inhibited by antagonists of alpha-2 adrenoceptors (yohimbine, rauwolscine and idazoxan) but not by alpha-1 antagonists (prazosin, corynanthine). Furthermore, an ex vivo receptor binding study in the rat showed that detomidine-induced decrease in spontaneous activity was significantly correlated to [3H]clonidine but not to [3H]prazosin displacement in brain membranes. These results show that detomidine has potent sedative effects in mice, rats and chicks, and suggest that this action is mediated through stimulation of alpha-2 adrenoceptors.
在实验动物中研究了新型咪唑衍生物地托咪定的镇静作用及其作用机制。采用三种方法来量化药物诱导的镇静作用：（i）小鼠自发活动的减少；（ii）小鼠巴比妥类药物诱导麻醉时间的延长；（iii）雏鸡翻正反射的消失。研究中纳入可乐定和赛拉嗪作为对照。结果表明，地托咪定的镇静效力与可乐定大致相当，远高于赛拉嗪。在所有试验中，地托咪定的镇静作用均被α-2肾上腺素能受体拮抗剂（育亨宾、萝芙素和咪唑克生）抑制，但未被α-1拮抗剂（哌唑嗪、育亨宾碱）抑制。此外，大鼠的一项体外受体结合研究表明，地托咪定诱导的自发活动减少与[3H]可乐定在脑膜中的置换显著相关，而与[3H]哌唑嗪的置换无关。这些结果表明，地托咪定在小鼠、大鼠和雏鸡中具有强效镇静作用，提示该作用是通过刺激α-2肾上腺素能受体介导的。
