Koenig-Berard E, Tierney C, Beau B, Delbarre G, Lhoste F, Labrid C
Institut de Recherches Internationales Servier, Neuilly-sur-Seine, France.
Am J Cardiol. 1988 Feb 24;61(7):22D-31D. doi: 10.1016/0002-9149(88)90460-2.
Rilmenidine (S 3341) is a new alpha 2 agonist, with antihypertensive properties. Pharmacologic data concerning its hemodynamic and central nervous system effects in the rat are described in this report. In the anesthetized or conscious spontaneously hypertensive rat, rilmenidine was found effective and potent as an antihypertensive agent, lowering blood pressure in a dose-dependent manner after intravenous and oral administration. These effects are related to a reduction in sympathetic tone as seen by the decrease in plasma catecholamines induced by rilmenidine in the spontaneously hypertensive rat. Studies in the normotensive pithed rat (electrical stimulation and adrenalectomization) confirmed the presynaptic alpha 2-stimulating properties of rilmenidine and suggested that a component of the antihypertensive activity of rilmenidine could be exerted through these peripheral receptors. A study of the central effects of rilmenidine was performed using classic neuropharmacologic tests. No effect was observed on the pentobarbitone-induced sleeping time in the rat. Rilmenidine caused only a minimal and non-dose-dependent inhibition of the righting reflex in the chick. In the rat, rilmenidine did not decrease the motor activity at concentrations up to 50 times higher than the antihypertensive dose. These results confirmed the contrast between rilmenidine and clonidine and suggest that a dissociation between sedative and antihypertensive effects could occur with rilmenidine.
利美尼定（S 3341）是一种新型α2激动剂，具有抗高血压特性。本报告描述了其对大鼠血液动力学和中枢神经系统作用的药理学数据。在麻醉或清醒的自发性高血压大鼠中，发现利美尼定作为一种抗高血压药物有效且强效，静脉内和口服给药后均能以剂量依赖方式降低血压。这些作用与交感神经张力降低有关，如利美尼定可使自发性高血压大鼠血浆儿茶酚胺减少。在正常血压的去脑大鼠（电刺激和肾上腺切除）中进行的研究证实了利美尼定的突触前α2刺激特性，并表明利美尼定的抗高血压活性部分可通过这些外周受体发挥作用。使用经典神经药理学试验对利美尼定的中枢作用进行了研究。未观察到利美尼定对大鼠戊巴比妥诱导睡眠时间的影响。利美尼定仅对雏鸡的翻正反射产生最小且非剂量依赖性的抑制。在大鼠中，利美尼定在浓度高达抗高血压剂量50倍时并未降低运动活性。这些结果证实了利美尼定与可乐定之间的差异，并表明利美尼定可能会出现镇静作用与抗高血压作用的分离。
