Ollivier J P, Christen M O
Hôpital d'Instruction des Armées du Val-de-Grace, Paris, France.
J Cardiovasc Pharmacol. 1994;24 Suppl 1:S39-48. doi: 10.1097/00005344-199424001-00008.
Although essential hypertension is usually defined as a hemodynamic disorder, it is expressed differently among individuals and varies during progression of the disease state. Therefore, various types of treatment can be envisioned. The use of selective I1-imidazoline-receptor agonists to modulate I1-imidazoline receptors involved in the central regulation of blood pressure has led to the introduction of a novel class of centrally acting antihypertensive drugs. Moxonidine, a representative molecule of this class, dissociates between a 10% alpha 2-adrenoceptor-agonist action linked with side effects such as fatigue or dry mouth, and a 90% specific antihypertensive action resulting from its selective agonistic action at I1-imidazoline receptors. Clinical experience is based on more than 2,000 patients and volunteers, and long-term efficacy has been demonstrated in about 500 patients who received a daily dose of moxonidine 0.2-0.4 mg. Moxonidine produces a pronounced reduction in peripheral vascular resistance without reflex tachycardia, accompanied by reduced plasma norepinephrine concentration and plasma-renin activity. Cardiovascular responses to exercise and standing remain nearly normal, and serious or life-threatening side effects, particularly the sympathetic overactivity that can occur on sudden withdrawal of other centrally acting agents, are never observed. In addition, moxonidine behaves neutrally with respect to plasma levels of cholesterol, potassium and glucose, glucose and lipid metabolism, and renal function, and can be administered without complication to patients with asthma or certain other diseases. Studies with magnetic resonance imaging have shown that moxonidine significantly reduces left ventricular mass, an indicator of left ventricular hypertrophy (LVH), within a 6-month treatment period, an effect that coincided with decreased plasma concentrations of catecholamines and renin. Comparisons between moxonidine and other well-established antihypertensive drugs such as nifedipine, atenolol, or angiotensin-converting enzyme inhibitors showed equal effectiveness in lowering blood pressure, whereas the adverse events profile always favored moxonidine. Considering its efficacy, safety, and specific effects (e.g., its ability to reduce LVH), moxonidine meets the criteria satisfied by other currently prescribed antihypertensive drugs. Because of its especially favorable benefit-to-risk ratio, moxonidine should be recommended as first-line treatment of hypertension and may also be useful in treating related problems such as LVH, coronary artery disease, and ventricular premature beats.
尽管原发性高血压通常被定义为一种血液动力学紊乱，但它在个体之间表现不同，并且在疾病进展过程中也会发生变化。因此，可以设想多种治疗方式。使用选择性I1-咪唑啉受体激动剂来调节参与血压中枢调节的I1-咪唑啉受体，已促使一类新型的中枢性抗高血压药物问世。莫索尼定是这类药物的代表分子，它在与诸如疲劳或口干等副作用相关的10%的α2-肾上腺素能受体激动作用和因其对I1-咪唑啉受体的选择性激动作用而产生的90%的特异性抗高血压作用之间存在解离。临床经验基于2000多名患者和志愿者，在约500名每日服用0.2 - 0.4毫克莫索尼定的患者中已证明了其长期疗效。莫索尼定可显著降低外周血管阻力，且无反射性心动过速，同时伴有血浆去甲肾上腺素浓度和血浆肾素活性降低。对运动和站立的心血管反应几乎保持正常，并且从未观察到严重或危及生命的副作用，特别是在突然停用其他中枢性药物时可能出现的交感神经过度活动。此外，莫索尼定对血浆胆固醇、钾和葡萄糖水平、葡萄糖和脂质代谢以及肾功能呈中性作用，并且可以无并发症地给予哮喘或某些其他疾病患者。磁共振成像研究表明，在6个月的治疗期内，莫索尼定可显著降低左心室质量，这是左心室肥厚（LVH）的一个指标，该效应与儿茶酚胺和肾素的血浆浓度降低相一致。莫索尼定与其他成熟的抗高血压药物如硝苯地平、阿替洛尔或血管紧张素转换酶抑制剂之间的比较表明，在降低血压方面效果相当，而不良事件谱总是有利于莫索尼定。考虑到其疗效、安全性和特定作用（例如其降低LVH的能力），莫索尼定符合目前其他处方抗高血压药物所满足的标准。由于其特别有利的效益风险比，莫索尼定应被推荐为高血压的一线治疗药物，并且在治疗相关问题如LVH、冠状动脉疾病和室性早搏方面可能也有用。
