A lipophilic, selective α1 -adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587)
A lipophilic, selective α1 -adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587)
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亲脂性、选择性 α1-肾上腺素受体激动剂：2-(2-氯-5-三氟甲基苯基亚氨基)咪唑烷 (St 587)
DOI：
10.1016/0024-3205(81)90648-2
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发表时间：
1981
期刊：
影响因子：
6.1
通讯作者：
P. A. Zwieten
中科院分区：
文献类型：
--
作者：
A. Jonge;J. V. Meel;P. Timmermans;P. A. Zwieten
描述了一种新化合物 (St 587)，它是一种具有亲脂性的选择性 α1-肾上腺素受体刺激剂。这种特性的组合是新颖的，因为迄今为止开发的所有α1-肾上腺素受体激动剂都是亲水性的。在几种动物模型中研究了可乐定衍生物 2-(2-氯-5-三氟甲基苯基亚氨基)咪唑烷 (St 587) 的 α-肾上腺素能作用。 St 587（1-10,000 μg/kg，静脉注射）可在血压正常的大鼠中诱导血管收缩。这种外周升压活性被哌唑嗪 (0.1 mg/kg) 强烈拮抗，但不受育亨宾 (1 mg/kg) 影响。在完整的、戊巴比妥麻醉的正常血压大鼠中，St 587（1-3,000 μg/kg，静脉注射）会引起短暂的升压反应，但没有观察到血压和心率的继发性下降。在剧烈运动的大鼠中，St 587（1-1,000 μg/kg）未能改变心脏加速器交感神经纤维电刺激产生的心率增加。当注射到麻醉猫的左侧椎动脉时，St 587（300 和 1,000 μg/kg）没有表现出中枢性降血压活性。此外，当静脉注射 St 587 时，没有观察到降压作用。用于麻醉血压正常的大鼠和猫。在小鼠中，St 587（10-10,000 μg/kg，腹腔注射）缺乏镇静特性，因为它不会延长己巴比妥（75 mg/kg，腹腔注射）引起的翻正反射丧失。在 37°C 的辛醇/缓冲液 (pH=7.4) 参考系统中，St 587 的总体亲脂性 (log P') 为 1.54。实验数据表明St 587是一种具有选择性α1-激动活性的亲脂性化合物。 St 587 不能引起低血压和镇静，这为以下观点提供了进一步的证据：大脑中的α1-肾上腺素受体不参与由可乐定和相关药物引起的中枢降血压作用和镇静作用。这些效应仅由α2-肾上腺素受体同质群体介导。
A new compound (St 587) is described, which is a selectiveα1-adrenoceptor stimulating agent with lipophilic properties. This combination of characteristics is novel, since allα1-adrenoceptor agonists developed so far are hydrophilic. The α-adrenergic effects of 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), a derivative of clonidine, were examined in several animal models. St 587 (1–10,000 μg/kg, i.v.) induced vasoconstriction in pithed, normotensive rats. This peripheral pressor activity was strongly antagonized by prazosin (0.1 mg/kg), but not affected by yohimbine (1 mg/kg). In intact, pentobarbitone-anaesthetized normotensive rats, St 587 (1–3,000 μg/kg, i.v.) evoked transient pressor responses, but a secondary fall in blood pressure and cardiac frequency was not observed. In pitched rats, St 587 (1–1,000 μg/kg) failed to modify the increase in heart rate produced by electrical stimulation of the cardioaccelerator sympathetic nerve fibres. St 587 (300 and 1,000 μg/kg) did not display central hypotensive activity, when injected into the left vertebral artery of anaesthetized cats. In addition, no hypotensive effect was observed when St 587 was administered i.v. to anaesthetized normotensive rats and cats. In mice, St 587 (10–10,000 μg/kg, i.p.) lacked sedative properties, since it did not prolong the hexobarbitone (75 mg/kg, i.p.)-induced loss of the righting reflex. The overall lipophilicity (log P′) of St 587 in the octanol/buffer (pH=7.4) reference system at 37°C amounted to 1.54. The experimental data suggest that St 587 is a lipophillic compound with selectiveα1- agonistic activity. The inability of St 587 to cause hypotension and sedation provides further evidence for the view thatα1-adrenoceptors in the brain are not involved in the central hypotensive action and the sedation, caused by clonidine and related drugs. These effects are solely mediated by homogenous populations ofα2-adrenoceptors.
20世纪80年代以来家庭消费和资产的实证分析
DOI：
--
发表时间：
2006
期刊：
総務省統計研修所 リサーチペーパー 第5号
影响因子：
--
作者：
元山 斉;山口 幸三;ryoko Morozumi;美添泰人・荒木万寿夫
通讯作者：
美添泰人・荒木万寿夫