Razzak A, Kawasaki H, Ueki S
Jpn J Pharmacol. 1977 Jun;27(3):437-44. doi: 10.1254/jjp.27.437.
Clonidine at doses of 0.5-1.0 mg/kg i.p. produced an initial rise followed by a sustained fall in blood pressure. The initial pressor response became more marked and the onset of hypotensive effect was delayed as the dose was increased to large doses such as 10-50 mg/kg given intraperitoneally. The heart rate was markedly reduced soon after clonidine administration and the bradycardia lasted for more than 2 hours. Both the initial pressor and subsequent hypotensive effects of clonidine were reduced by pretreatment with phentolamine, the initial pressor effects were suppressed by propranolol which did not affect the hypotensive effects. This initial pressor effect was potentiated while the hypotensive effect was reduced after bilateral vagotomy and pretreatment with either 6-hydroxydopamine or atropine. The bradycardia was significantly reduced by propranolol, atropine and bilateral vagotomy. Central sympathetic as well as parasympathetic mechanisms may be involved in cardiovascular changes after large doses of clonidine in urethanized mice.
腹腔注射剂量为0.5 - 1.0毫克/千克的可乐定，会使血压先升高，随后持续下降。随着腹腔注射剂量增加至大剂量，如10 - 50毫克/千克，最初的升压反应变得更加明显，而降压作用的起效时间延迟。给予可乐定后不久，心率显著降低，且心动过缓持续超过2小时。酚妥拉明预处理可降低可乐定最初的升压作用和随后的降压作用，普萘洛尔可抑制最初的升压作用，但不影响降压作用。双侧迷走神经切断术以及用6 - 羟基多巴胺或阿托品预处理后，最初的升压作用增强，而降压作用减弱。普萘洛尔、阿托品和双侧迷走神经切断术可显著减轻心动过缓。在乌拉坦麻醉的小鼠中，大剂量可乐定后的心血管变化可能涉及中枢交感神经以及副交感神经机制。
