Kawasaki H
Department of Clinical Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Okayama University.
Nihon Rinsho. 1997 Aug;55(8):2081-5.
The blood pressure is maintained by the tonic vasomotor activity of efferent sympathetic neurons which are tonically regulated by the rostral ventrolateral medulla (RVLM) in the brain. The alpha 2-adrenoceptor agonist such as clonidine, guanabenz and guanfacine, acts on RVLM to decrease sympathetic neuron activity and lower blood pressure. Drug such as alpha-methyldopa, through its metabolite alpha-methylnoradrenaline, acts like clonidine as an alpha 2-adrenoceptor agonist in the brain. Clonidine and allied drugs except for alpha-methyldopa also bind to imidazoline receptors, which is believed to mediate the hypotensive action. The centrally acting antihypertensive drugs are used for treatment of moderate to severe forms of hypertension and are effective in patients with renal failure. The treatment with these drugs induces central nervous system side effect of sedation and drowsiness, which limits the clinical usefulness and are believed to be mediated by central alpha 2-adrenoceptors. The new imidazoline compounds, rilmenidine and moxonidine, which selectively act on imidazoline receptors, may be a useful antihypertensive drug without such central side effects.
血压由传出交感神经元的紧张性血管运动活动维持，而这些神经元受脑内头端腹外侧延髓（RVLM）的紧张性调节。α2肾上腺素能受体激动剂，如可乐定、胍那苄和胍法辛，作用于RVLM以降低交感神经元活性并降低血压。药物如α-甲基多巴，通过其代谢产物α-甲基去甲肾上腺素，在脑内作为α2肾上腺素能受体激动剂发挥作用，类似于可乐定。除α-甲基多巴外，可乐定及相关药物还与咪唑啉受体结合，据信该受体介导降压作用。中枢性抗高血压药物用于治疗中度至重度高血压，对肾衰竭患者有效。使用这些药物进行治疗会引起镇静和嗜睡等中枢神经系统副作用，这限制了其临床应用，且据信这些副作用是由中枢α2肾上腺素能受体介导的。新型咪唑啉化合物，利美尼定和莫索尼定，它们选择性作用于咪唑啉受体，可能是一种没有此类中枢副作用的有用抗高血压药物。
