Roach A G, Doxey J C, Strachan D A, Cavero I
J Pharmacol Exp Ther. 1983 Nov;227(2):421-8.
The ability of a series of alpha adrenoceptor agonists to induce a sleep-like state (as measured by the time interval between the loss and regaining of the righting reflex) has been assessed in 2-day-old chicks in order to understand their pharmacological profile better. Guanabenz, guanoxabenz, UK-14,304, guanfacine and xylazine produced dose-related increases in sleeping time, the highest dose of these agonists causing the chicks to sleep for over 120 min. In contrast, the dose-response curves to tiamenidine and clonidine were flatter and bell-shaped with maxima of 30 and 60 min, respectively. The effects of all these compounds were antagonized by idazoxan (RX781094) and yohimbine (two selective alpha-2 adrenoceptor antagonists) but were moderately enhanced or unaffected by prazosin (a selective alpha-1 adrenoceptor antagonist) confirming that the state of arousal in chicks can be depressed by stimulation of alpha-2 adrenoceptors. In particular, idazoxan displaced significantly the guanoxabenz dose-response curve to the right without affecting its slope and apparent maximum and blocked the sleep induced by clonidine. However, idazoxan failed to affect the sleep evoked by ethanol, etorphine or pentobarbital. Naloxone antagonized the effects of etorphine but not those of guanoxabenz, ethanol or pentobarbital. The relatively selective alpha-1 adrenoceptor agonist, cirazoline, given in doses up to 20 mg/kg i.m., produced in chicks behavioral manifestations suggestive of enhanced arousal.(ABSTRACT TRUNCATED AT 250 WORDS)
为了更好地了解一系列α肾上腺素能受体激动剂的药理学特性,研究人员在2日龄雏鸡中评估了它们诱导睡眠样状态的能力(通过翻正反射丧失和恢复之间的时间间隔来衡量)。胍那苄、胍氧苄、UK-14,304、胍法辛和赛拉嗪可使睡眠时间呈剂量依赖性增加,这些激动剂的最高剂量可使雏鸡睡眠超过120分钟。相比之下,噻美尼定和可乐定的剂量反应曲线较平缓且呈钟形,最大值分别为30分钟和60分钟。所有这些化合物的作用均被咪唑克生(RX781094)和育亨宾(两种选择性α-2肾上腺素能受体拮抗剂)拮抗,但被哌唑嗪(一种选择性α-1肾上腺素能受体拮抗剂)适度增强或未受影响,这证实了刺激α-2肾上腺素能受体可降低雏鸡的觉醒状态。特别是,咪唑克生使胍氧苄的剂量反应曲线显著右移,而不影响其斜率和表观最大值,并阻断了可乐定诱导的睡眠。然而,咪唑克生未能影响乙醇、埃托啡或戊巴比妥诱导的睡眠。纳洛酮拮抗了埃托啡的作用,但不影响胍氧苄、乙醇或戊巴比妥的作用。相对选择性的α-1肾上腺素能受体激动剂西拉唑啉,肌肉注射剂量高达20mg/kg时,在雏鸡中产生了提示觉醒增强的行为表现。(摘要截短于250字)