Weinstock M, Zavadil A P, Rosin A J, Chiueh C C, Kopin I J
J Pharmacol Exp Ther. 1978 Jul;206(1):91-6.
Oxotremorine, 0.25 mg/kg, produces marked tremor in the rat, which is abolished by scopolamine, 0.5 mg/kg, and is substantially reduced in intensity and duration both by adrenalmedullectomy and by chemical sympathectomy with 6-hydroxydopamine. Oxotremorine increases plasma norepinephrine from 0.62 +/- 0.07 to 3.01 +/- 0.47 ng/ml and plasma epinephrine, from 0.82 +/- 0.14 to 3.42 +/- 0.48 ng/ml, in conscious unrestrained rats. l-Propranolol (0.5-2.5 mg/kg) reduces tremor, and at 2.5 mg/kg is more effective than either chemical sympathectomy or adrenal demedullation. d-Propranolol and sotalol are also active at 4 and 10 times the dose of l-propranolol, respectively. l-Propranolol does not prevent the rise in catecholamines induced by oxotremorine. It is suggested that stimulation of central muscarinic receptors causes tremor by a combination of two effects. There is an increase in cholinergic influence to motor efferents accompanied by an activation of the sympathoadrenal system to release catecholamines which augment tremor by stimulation of beta2 adrenoceptors.
毒蕈碱(0.25毫克/千克)可使大鼠产生明显震颤,而0.5毫克/千克的东莨菪碱可消除这种震颤。肾上腺髓质切除术以及用6-羟基多巴胺进行化学性交感神经切除术后,震颤的强度和持续时间均显著降低。在清醒自由活动的大鼠中,毒蕈碱可使血浆去甲肾上腺素从0.62±0.07纳克/毫升升至3.01±0.47纳克/毫升,使血浆肾上腺素从0.82±0.14纳克/毫升升至3.42±0.48纳克/毫升。左旋普萘洛尔(0.5 - 2.5毫克/千克)可减轻震颤,2.5毫克/千克时比化学性交感神经切除术或肾上腺髓质切除术更有效。右旋普萘洛尔和索他洛尔的活性分别为左旋普萘洛尔剂量的4倍和10倍。左旋普萘洛尔不能阻止毒蕈碱引起的儿茶酚胺升高。有人提出,中枢毒蕈碱受体的刺激通过两种效应的组合导致震颤。胆碱能对运动传出神经的影响增加,同时交感肾上腺系统激活以释放儿茶酚胺,儿茶酚胺通过刺激β2肾上腺素能受体增强震颤。