Oparil S
Clin Exp Hypertens A. 1982;4(4-5):579-93. doi: 10.3109/10641968209061600.
The brain influences arterial pressure through central mediation of a variety of neurotransmitters, including norepinephrine, and translates this action into changes in peripheral autonomic tone. Two opposed adrenergic systems have been described in brain: a hypothalamic pathway in which adrenergic receptor stimulation raises arterial pressure and a brainstem pathway related to the baroreflex arc in which adrenergic receptor stimulation lowers arterial pressure. Antihypertensive drugs with primarily central effects, including clonidine and alpha methyldopa, act as alpha 2 adrenoceptor agonists. The central receptor involved in their antihypertensive action is of the alpha 2 type but is located postsynaptically. Activation of this receptor by either clonidine or alpha methylnorepinephrine, a metabolite of alpha methyldopa, engages the depressor pathway in the brainstem and leads to a decrease in norepinephrine release and a reduction in peripheral sympathetic tone. Clonidine and alpha methyldopa share a similar pattern of peripheral effects, including reductions in preganglionic sympathetic nerve traffic, bradycardia, decreases in plasma renin activity, reductions in blood pressure in the supine position and adverse effects such as depression, sedation and bad dreams. Because of the frequency and severity of these side effects, there is an ongoing search for new centrally acting antihypertensive agents which might be better tolerated.
大脑通过多种神经递质（包括去甲肾上腺素）的中枢调节来影响动脉血压，并将这种作用转化为外周自主神经张力的变化。大脑中已描述了两种相反的肾上腺素能系统：一种是下丘脑途径，其中肾上腺素能受体刺激会升高动脉血压；另一种是与压力反射弧相关的脑干途径，其中肾上腺素能受体刺激会降低动脉血压。主要具有中枢作用的抗高血压药物，包括可乐定和α-甲基多巴，作为α2肾上腺素能受体激动剂起作用。参与其抗高血压作用的中枢受体是α2型，但位于突触后。可乐定或α-甲基多巴的代谢产物α-甲基去甲肾上腺素激活该受体，会激活脑干中的降压途径，导致去甲肾上腺素释放减少和外周交感神经张力降低。可乐定和α-甲基多巴具有相似的外周效应模式，包括节前交感神经活动减少、心动过缓、血浆肾素活性降低、仰卧位血压降低以及诸如抑郁、镇静和噩梦等不良反应。由于这些副作用的发生频率和严重程度，人们一直在寻找耐受性可能更好的新型中枢性抗高血压药物。
