Prichard B N, Graham B R, Owens C W
Centre of Clinical Pharmacology, University College London, UK.
J Hypertens Suppl. 1999 Aug;17(3):S41-54.
Moxonidine is a centrally acting antihypertensive. Its action is mediated by imidazoline I1 receptors located in the rostral ventro-lateral medulla (RVLM). Animal experiments show that much smaller amounts are required to reduce blood pressure (BP) when it is given intracisternally, or injected directly into the RVLM, compared to intravenous dose. Pretreatment with imidazoline I1 blockade from efaroxan abolishes the antihypertensive action of microinjection of moxonidine into the RVLM in the spontaneously hypertensive rat (SHR), while alpha2 blockade from SKF 86466 is much less effective. Microinjection of efaroxan into the RVLM prevents the fall of BP in the SHR from intravenous moxonidine. Moxonidine binds with an affinity for the imidazoline I1 receptor that is 33 times more effective than is alpha2-receptor binding. There is only a few fold preference for binding at the imidazoline I1-receptor for clonidine. Moxonidine results in a fall in adrenaline, noradrenaline and renin levels in humans, as might be expected from central inhibition of sympathetic tone. Moxonidine gives a fall of BP due to a decline in systemic vascular resistance, while the heart rate, cardiac output, stroke volume and pulmonary artery pressures are not affected. There is a reduction in left-ventricular end systolic and diastolic volumes. There is a regression of left-ventricular hypertrophy after moxonidine was given for 6 months. Following oral administration the half-life (Tmax) is about 1 h. Moxonidine is highly bioavailable, approaching 90%. Moxonidine is largely excreted unchanged, biotransformation is unimportant. It has a T(1/2) of 2.5 h, renal insufficiency prolongs the T(1/2). However, suggesting possible retention in the central nervous system (CNS) the antihypertensive effect lasts longer than would be expected from the half-life. Moxonidine has been shown to be suitable for administration once daily. Moxonidine is an effective antihypertensive drug. In the course of its evaluation it has been compared with representatives from each important class of antihypertensive drugs, with diuretics, both alpha- and beta-blocking drugs, clonidine, calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors. These studies have shown that BP control is overall similar with moxonidine and these other agents. Moxonidine has a favourable side-effect profile, at least in part due to its lack of effect on central alpha2 receptors.
莫索尼定是一种中枢性抗高血压药。其作用是通过位于延髓头端腹外侧（RVLM）的咪唑啉I1受体介导的。动物实验表明，与静脉给药剂量相比，当通过脑池内给药或直接注射到RVLM时，所需降低血压（BP）的剂量要小得多。预先用依伐罗新进行咪唑啉I1阻断，可消除向自发性高血压大鼠（SHR）的RVLM微量注射莫索尼定的抗高血压作用，而用SKF 86466进行α2阻断的效果则要差得多。向SHR的RVLM微量注射依伐罗新可防止静脉注射莫索尼定后血压下降。莫索尼定与咪唑啉I1受体的结合亲和力比与α2受体结合的亲和力高33倍。与可乐定相比，莫索尼定对咪唑啉I1受体的结合仅有几倍的偏好性。正如从对交感神经张力的中枢抑制所预期的那样，莫索尼定可使人体肾上腺素、去甲肾上腺素和肾素水平下降。莫索尼定由于全身血管阻力下降而导致血压下降，而心率、心输出量、每搏输出量和肺动脉压不受影响。左心室收缩末期和舒张末期容积减小。给予莫索尼定6个月后，左心室肥厚有所消退。口服给药后半衰期（Tmax）约为1小时。莫索尼定的生物利用度很高，接近90%。莫索尼定大部分以原形排泄，生物转化并不重要。其半衰期（T1/2）为2.
