Dominiak P
Institute of Pharmacology, Medical University of Lübeck, Germany.
Cardiovasc Drugs Ther. 1994 Mar;8 Suppl 1:21-6. doi: 10.1007/BF00877081.
The central nervous system is involved in the control of arterial blood pressure. Stimulation of central alpha 2-adrenoceptors in the nucleus tractus solitarii (NTS) decreases sympathetic outflow, resulting in a fall in arterial blood pressure. One of the first antihypertensive substances with actions on the alpha 2-adrenoceptors of the NTS was alpha-methylnoradrenaline. Later on the imidazoline clonidine was developed for which numerous effects, mediated by alpha 2-adrenoceptors, in the CNS could be demonstrated. Since the centrally acting alpha 2-adrenoceptor agonists possess severe side effects, the development of more specific and selective centrally acting imidazolines resulted in the derivatives moxonidine and rilmenidine. The effects of the "second-generation imidazolines" could not be fully understood as alpha 2-adrenoceptor agonists. In the meantime, the rostral ventrolateral medulla (RVLM) has been identified as the site of action of the imidazolines and an I1-imidazoline binding site was characterized in this region. For the antihypertensive action of the imidazolines, agonism at the I1-imidazoline subtype seems to be responsible. In addition, an acid- and heat-stable endogenous substance, called clonidine displacing substance (CDS), was reported to bind at the putative I receptor. In 1992 a receptor protein for I receptors (70 kD) could be separated that is different from that of alpha 2-adrenoceptors. However, up to now we are still lacking the amino-acid sequence of the I receptor and its second messenger system.
中枢神经系统参与动脉血压的调控。刺激孤束核（NTS）中的中枢α2 - 肾上腺素能受体可减少交感神经输出，导致动脉血压下降。最早作用于NTS的α2 - 肾上腺素能受体的抗高血压物质之一是α - 甲基去甲肾上腺素。后来开发了咪唑啉类药物可乐定，其在中枢神经系统中的多种效应可由α2 - 肾上腺素能受体介导。由于中枢作用的α2 - 肾上腺素能受体激动剂具有严重的副作用，因此开发了更具特异性和选择性的中枢作用咪唑啉类药物，即莫索尼定和利美尼定。“第二代咪唑啉类药物”的作用不能完全被理解为α2 - 肾上腺素能受体激动剂。与此同时，延髓头端腹外侧区（RVLM）已被确定为咪唑啉类药物的作用部位，并且在该区域鉴定出了一个I1 - 咪唑啉结合位点。对于咪唑啉类药物的抗高血压作用，似乎是I1 - 咪唑啉亚型的激动作用起了作用。此外，据报道有一种酸和热稳定的内源性物质，称为可乐定置换物质（CDS），可与假定的I受体结合。1992年，一种与α2 - 肾上腺素能受体不同的I受体（70 kD）的受体蛋白被分离出来。然而，到目前为止，我们仍然缺乏I受体的氨基酸序列及其第二信使系统。
