van Zwieten P A
Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
Clin Exp Hypertens. 1996 Apr-May;18(3-4):291-303. doi: 10.3109/10641969609088964.
The modulation of peripheral sympathetic activity by the central nervous system may involve various pathways, neurotransmitters and receptors. In particular central catecholaminergic neurones and alpha-adrenoceptors have been analysed in detail, and they are recognized as important targets of the classic centrally acting antihypertensives clonidine, guanfacine and alpha-methyl-DOPA. Initially these drugs have been assumed to reduce elevated blood pressure via the stimulation of central alpha 2-adrenoceptors in the brain stem, thus leading to peripheral sympathoinhibition and a reduction of elevated blood pressure, heart rate and plasma catecholamines. In a later stage it has been recognized that central imidazoline (I1) receptors, probably located in the nucleus reticularis lateralis in the medullary region may also be involved in the central regulation of peripheral sympathetic activity, and for that matter as a target of centrally acting antihypertensives. Moxonidine and rilmenidine are the prototypes of such agents. Accordingly, the receptor profile of the various types of centrally acting antihypertensives may be characterized as follows: [formula: see text] The various compounds mentioned will thus cause peripheral sympathoinhibition, initiated by different receptor targets in the CNS. Finally, the peripheral alpha 1-blocker urapidil has been demonstrated to possess an additional central mechanism, mediated by the stimulation of serotonergic 5HT1A-receptors located in the rostral ventrolateral medulla.
中枢神经系统对外周交感神经活动的调节可能涉及多种途径、神经递质和受体。特别是中枢儿茶酚胺能神经元和α-肾上腺素能受体已得到详细分析，它们被认为是经典中枢性抗高血压药物可乐定、胍法辛和α-甲基多巴的重要作用靶点。最初，这些药物被认为是通过刺激脑干中的中枢α2-肾上腺素能受体来降低血压升高，从而导致外周交感神经抑制，并降低血压、心率和血浆儿茶酚胺水平。在后期，人们认识到中枢咪唑啉（I1）受体，可能位于髓质区域的外侧网状核，也可能参与外周交感神经活动的中枢调节，并且就此而言是中枢性抗高血压药物的作用靶点。莫索尼定和利美尼定是这类药物的代表。因此，各种类型的中枢性抗高血压药物的受体谱可描述如下：[公式：见原文]因此，上述各种化合物将通过中枢神经系统中不同的受体靶点引发外周交感神经抑制。最后，已证明外周α1-阻滞剂乌拉地尔具有一种额外的中枢机制，该机制由位于延髓头端腹外侧的5-羟色胺能5HT1A受体的刺激介导。
