Schachter M, Luszick J, Jäger B, Verboom C, Söhlke E
Clinical Pharmacology, Imperial College School of Medicine, St Mary's Hospital, London, England.
Drug Saf. 1998 Sep;19(3):191-203. doi: 10.2165/00002018-199819030-00003.
Classical centrally acting antihypertensive agents lower blood pressure by reducing excessive sympathetic tone; however, their clinical use is limited by an adverse effect profile resulting from alpha2-adrenoceptor agonism. Moxonidine is a new centrally acting agent showing selective agonism of imidazoline I1 receptors, but very little alpha2-adrenoceptor agonism. The safety and tolerability of moxonidine was reviewed over an 8-year period (1989 to 1997), including 74 clinical trials and an estimated 370000 patient-years of exposure. Dry mouth and somnolence were the most frequently reported adverse events, followed by headache and dizziness. In phase II to IV controlled studies in patients with hypertension (n = 1460), the incidence of dry mouth was 8 to 9%, somnolence 5 to 8% and headache 6%, as recorded by spontaneous reporting; the percentage of patients discontinuing treatment because of adverse events did not exceed 4%. Subgroup analyses revealed no differences in adverse events related to age or gender. Moxonidine did not exacerbate concomitant conditions such as diabetes mellitus or chronic obstructive pulmonary disease, or interact pharmacokinetically with concurrent medications such as hydrochlorothiazide, digoxin and glibenclamide (glyburide). Coadministration of moxonidine with lorazepam resulted in small additional impairments in tasks requiring attention. A similar distribution of adverse events was observed in uncontrolled studies (n = 1058). The incidence and severity of dry mouth and somnolence were found to decrease with increasing exposure to moxonidine over a period of up to 2 years. Serious adverse events were rare in all trials and could not be attributed to administration of moxonidine. Post-marketing surveillance of the adverse effect profile of moxonidine detected 2 additional adverse effects: nausea and allergic skin reactions. The safety profile of moxonidine, combined with proven antihypertensive efficacy, suggests that it may have an important role to play in the management of mild-to-moderate hypertension.
经典的中枢性抗高血压药物通过降低过度的交感神经张力来降低血压；然而，它们的临床应用受到α2-肾上腺素能受体激动引起的不良反应的限制。莫索尼定是一种新型的中枢性药物，显示出对咪唑啉I1受体的选择性激动作用，但对α2-肾上腺素能受体的激动作用很小。在8年期间（1989年至1997年）对莫索尼定的安全性和耐受性进行了综述，包括74项临床试验和估计370000患者年的暴露量。口干和嗜睡是最常报告的不良事件，其次是头痛和头晕。在高血压患者的II至IV期对照研究（n = 1460）中，通过自发报告记录，口干的发生率为8%至9%，嗜睡为5%至8%，头痛为6%；因不良事件而停药的患者百分比不超过4%。亚组分析显示，与年龄或性别相关的不良事件没有差异。莫索尼定不会加重诸如糖尿病或慢性阻塞性肺疾病等并发疾病，也不会与同时使用的药物如氢氯噻嗪、地高辛和格列本脲（优降糖）发生药代动力学相互作用。莫索尼定与劳拉西泮合用会导致在需要注意力的任务中出现轻微的额外损害。在非对照研究（n = 1058）中观察到类似的不良事件分布。发现口干和嗜睡的发生率和严重程度会随着长达2年的莫索尼定暴露时间增加而降低。在所有试验中严重不良事件很少见，且不能归因于莫索尼定的给药。对莫索尼定不良反应的上市后监测发现了另外2种不良反应：恶心和过敏性皮肤反应。莫索尼定的安全性概况，结合已证实的抗高血压疗效，表明它可能在轻度至中度高血压的管理中发挥重要作用。
