Montastruc J L, Macquin-Mavier I, Damase-Michel C, Dard B, Tran M A, Valet P
Laboratoire de pharmacologie médicale et clinique, INSERM U 317, faculté de médecine, Toulouse.
Arch Mal Coeur Vaiss. 1989 Dec;82 Spec No 5:25-9.
Oral rilmenidine (1 mg/kg/day for 2 weeks) significantly reduces the blood pressure and heart rate of conscious barodenervated dogs. A dose-dependent decrease in blood pressure and heart rate has been demonstrated with intraveinous rilmenidine (0.1 to 1 mg/kg) in pentobarbitone anaesthetised spontaneously hypertensive rats (SHR). Chronic subcutaneous administration of rilmenidine (5 to 15 mg/kg/day) also produces a dose-dependent decrease of these two parameters in conscious SHR. In addition, rilmenidine reduces plasma noradrenaline and the liberation of catecholamines from the adrenal medulla; these actions could contribute to its antihypertensive effect. The hypotensive effect of rilmenidine, clonidine and related molecules, is due to a reduction in sympathetic tone of central or peripheral origin. Although rilmenidine binds to alpha-2 adrenergic receptors, it does not cause sedation in animal models: it does not prolong barbiturate-induced sleep in the mouse and rat at doses of up to 10 mg/kg and does not affect spontaneous locomotor activity in the rat at doses of up to 2.5 mg/kg. The results show a dissociation of the sedative and antihypertensive effects of rilmenadine. The almost complete absence of sedation in animal models may be explained by: as yet unknown properties inhibiting sedation, a preferential peripheral site of action and/or the presence of separate central receptors accounting for the sedative or hypotensive effects. The precise mechanism of the hypotensive effects of rilmenidine is currently under study. The binding of rilmenidine at central "imidazoline receptor" sites responsible for the regulation of the blood pressure could explain its mode of action and why its pharmacological profile is different to that of other centrally acting hypotensive agents.
口服利美尼定（1毫克/千克/天，持续2周）可显著降低清醒的去压力感受器神经犬的血压和心率。在戊巴比妥麻醉的自发性高血压大鼠（SHR）中，静脉注射利美尼定（0.1至1毫克/千克）已证明血压和心率呈剂量依赖性下降。慢性皮下注射利美尼定（5至15毫克/千克/天）也可使清醒SHR的这两个参数呈剂量依赖性下降。此外，利美尼定可降低血浆去甲肾上腺素水平，并减少肾上腺髓质儿茶酚胺的释放；这些作用可能有助于其降压效果。利美尼定、可乐定及相关分子的降压作用是由于中枢或外周交感神经张力降低。尽管利美尼定与α-2肾上腺素能受体结合，但在动物模型中它不会引起镇静作用：在高达10毫克/千克的剂量下，它不会延长小鼠和大鼠巴比妥酸盐诱导的睡眠时间，在高达2.5毫克/千克的剂量下，它不会影响大鼠的自发运动活性。结果显示利美尼定的镇静和降压作用存在分离。动物模型中几乎完全没有镇静作用可能是由于：尚未知晓的抑制镇静的特性、优先的外周作用部位和/或存在分别负责镇静或降压作用的中枢受体。利美尼定降压作用的确切机制目前正在研究中。利美尼定在负责血压调节的中枢“咪唑啉受体”部位的结合可以解释其作用方式，以及为什么其药理学特征与其他中枢性降压药物不同。
