Armah B I, Hofferber E, Stenzel W
Department of Pharmacology, BDF Research Laboratories, Hamburg, Fed. Rep. of Germany.
Arzneimittelforschung. 1988 Oct;38(10):1426-34.
Moxonidine (4-chloro-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methyl-5-pyrimidinamine, BDF 5895) reduces blood pressure and heart rate in rats with genetic hypertension (SHR/Okamoto) and in rats with renovascular hypertension (Goldblatt 1 k/1 c). The hypotensive action was also confirmed in renal-hypertensive dogs. The hypotensive action is preceded by a reduction in plasma noradrenaline concentration, thus reflecting a reduction in sympathetic activity. In anesthetized cats, administration of moxonidine into the vertebral artery induces a greater hypotensive effect than i.v. injection of same doses, indicating the central nervous system as the site of hypotensive action. Similar to clonidine, the hypotensive action of moxonidine is abolished by pretreatment of the animals with a selective alpha 2-antagonist. Direct application of moxonidine into the cisterna magna of anesthetized rabbits revealed a 10-fold greater hypotensive potency than clonidine, in contrast to i.v. application where moxonidine was 10-fold less potent than clonidine. At least 10-fold higher doses of moxonidine were needed to cause side effects (sedation, inhibition of gastric secretion), when compared with clonidine. Interruption of presynaptic noradrenergic pathways completely abolished the hypotensive action of moxonidine. Thus moxonidine is endowed with a specific central site of action, presumably by stimulating central presynaptic alpha 2-adrenoceptors. This specific central hypotensive action enables a greater dissociation between the antihypertensive effect on the one hand, and the side effects on the other.
莫索尼定（4-氯-N-（4,5-二氢-1H-咪唑-2-基）-6-甲氧基-2-甲基-5-嘧啶胺，BDF 5895）可降低遗传性高血压大鼠（SHR/冈本）和肾血管性高血压大鼠（戈德布拉特1k/1c）的血压和心率。在肾性高血压犬中也证实了其降压作用。降压作用之前血浆去甲肾上腺素浓度会降低，从而反映出交感神经活动的减少。在麻醉猫中，将莫索尼定注入椎动脉比静脉注射相同剂量产生的降压效果更强，表明中枢神经系统是降压作用的部位。与可乐定相似，用选择性α2拮抗剂预处理动物可消除莫索尼定的降压作用。将莫索尼定直接注入麻醉兔的小脑延髓池显示其降压效力比可乐定高10倍，而静脉注射时莫索尼定的效力比可乐定低10倍。与可乐定相比，至少需要高10倍剂量的莫索尼定才会引起副作用（镇静、抑制胃液分泌）。中断突触前去甲肾上腺素能途径可完全消除莫索尼定的降压作用。因此，莫索尼定具有特定的中枢作用部位，可能是通过刺激中枢突触前α2肾上腺素能受体实现的。这种特定的中枢降压作用使得一方面的降压效果与另一方面的副作用之间有更大的分离。
