rilmenidine心血管的影响,moxonidine和可乐定在有意识的野生型和D79N alpha2A-adrenoceptor转基因小鼠。

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小朱QM Lesnick JD,碧玉,•麦乐伦SJ,狄龙MP, Eglen RM,蓝色小博士

rilmenidine心血管的影响,moxonidine和可乐定在有意识的野生型和D79N alpha2A-adrenoceptor转基因小鼠。

Br J杂志。1999年3月,126 (6):1522 - 30。

PubMed ID

10217548 (在PubMed

]

文摘

1。我们调查rilmenidine的心血管效应,moxonidine和可乐定在有意识的野生型和D79N alpha2A-adrenoceptor老鼠。这些受体激动剂的体外药理学决心在重组(人类)alpha2-adrenoceptors和内源性alpha2A-adrenoceptors(狗)。2。在野生型小鼠,rilmenidine moxonidine(100年、300年和1000年microg公斤(1),注射)和可乐定(30、100年和300年microg公斤(1),注射)剂量依赖性降低血压和心率。3所示。在D79N alpha2A-adrenoceptor老鼠,应对rilmenidine和moxonidine没有不同于车辆控制。Clonidine-induced低血压是缺席,但剂量依赖性高血压和心动过缓观察。4所示。在野生型小鼠,应对moxonidine(1毫克公斤(1)、注射)的敌意的无选择性的,non-imidazoline alpha2-adrenoceptor拮抗剂,rs - 79948 - 197(1毫克公斤(1)、注射)。 5. Affinity estimates (pKi) at human alpha2A-, alpha2B- and alpha2C-adrenoceptors, respectively, were: rilmenidine (5.80, 5.76 and 5.33), moxonidine (5.37, <5 and <5) and clonidine (7.21, 7.16 and 6.87). In a [35S]-GTPgammaS incorporation assay, moxonidine and clonidine were alpha2A-adrenoceptor agonists (pEC50/intrinsic activity relative to noradrenaline): moxonidine (5.74/0.85) and clonidine (7.57/0.32). 6. In dog saphenous vein, concentration-dependent contractions were observed (pEC50/intrinsic activity relative to noradrenaline): rilmenidine (5.83/0.70), moxonidine (6.48/0.98) and clonidine (7.22/0.83). Agonist-independent affinities were obtained with RS-79948-197. 7. Thus, expression of alpha2A-adrenoceptors is a prerequisite for the cardiovascular effects of moxonidine and rilmenidine in conscious mice. There was no evidence of I1-imidazoline receptor-mediated effects. The ability of these compounds to act as alpha2A-adrenoceptor agonists in vitro supports this conclusion.

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药物靶点

药物	目标	类	生物	药理作用	行动
Moxonidine	Alpha-2A肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节
Rilmenidine	Alpha-2A肾上腺素能受体	蛋白质	人类	未知的	不可用	细节