Effects of putative α‐adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat
Effects of putative α‐adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat
复制标题
假定的α-肾上腺素受体拮抗剂和其他化合物对大鼠翻正反射丧失和赛拉嗪引起的眼球突出的影响
DOI：
10.1002/ddr.430070204
复制
发表时间：
1986
影响因子：
3.8
通讯作者：
F. Colpaert
中科院分区：
文献类型：
--
作者：
F. Colpaert
腹腔注射20 mg/kg甲苯噻嗪会导致大鼠翻正反射（LRR）丧失和眼球突出。实验确定了这些对甲苯噻嗪的反应的一些药理学特征。假定的α2-肾上腺素受体拮抗剂育亨宾、哌洛生、CGS 7525 A和咪唑克生阻断LRR反应;妥拉唑啉、酚妥拉明和沙丁胺醇在一定程度上减弱了该反应，而哌唑嗪、乙酰哌隆和酚苄明没有明显作用。在早期的研究中，假定的α2-激动剂可乐定、胍那苄、胍法辛、guanoxabenz、噻美尼定和萘甲唑啉在抑制大鼠行为中仅作为部分激动剂起作用，在本研究中发现其部分拮抗LRR反应。其他减弱但不阻断反应的化合物对α 2受体具有一定亲和力，并可能作为α2受体的部分拮抗剂（例如，酚妥拉明、LSD、麦角乙脲）或发挥一些唤醒或行为刺激作用（例如，可卡因、诺米芬辛、反苯环丙胺、阿扑吗啡）。唤醒感觉刺激也产生了LRR反应的部分衰减。甲苯噻嗪诱导的突眼似乎对假定的α1-拮抗剂哌唑嗪和乙酰哌隆有反应，其他发挥α1-拮抗剂活性的药物也可拮抗突眼。化合物拮抗大鼠中甲苯噻嗪诱导的LRR和突眼的剂量可提供化合物分别作为α 2-和α 1-肾上腺素受体拮抗剂的体内效力的估计。
Intraperitoneal injection of 20 mg/kg of xylazine causes loss of the righting reflex (LRR) and exophthalmia in the rat. The experiments determined some of the pharmacological characteristics of these responses to xylazine. The putative α2‐adrenoceptor antagonists yohimbine, piperoxan, CGS 7525 A, and idazoxan blocked the LRR response; tolazoline, phentolamine, and salbutamol attenuated the response to some extent, whereas prazosin, aceperone, and phenoxybenzamine exerted no apparent effect. The putative α2‐agonists clonidine, guanabenz, guanfacine, guanoxabenz, tiamenidine, and naphazoline were identified in an earlier study as acting only as partial agonists in depressing rat behavior and were found here to antagonize partially the LRR response. Other compounds that attenuated but did not block the response either have some affinity for and perhaps act as partial antagonists at α2‐receptors (e.g., phentolamine, LSD, lisuride) or exert some arousing or behaviorally stimulating action (e.g., cocaine, nomifensine, tranylcypromine, apomorphine). Arousing sensory stimulation also produced a partial attenuation of the LRR response. The xylazine‐induced exophthalmia appeared responsive to the putative α1‐antagonists prazosin and aceperone, and other drugs exerting α1‐antagonist activity also antagonized the exophthalmia. The doses at which compounds antagonize xylazine‐induced LRR and exophthalmia in rat might offer an estimate of the compounds' in vivo potency in acting as antagonists at a2‐ and a,‐adrenoceptors, respectively.