Pharmacodynamic and pharmacokinetic studies on prizidilol and nipradilol (K-351), antihypertensive drugs with combined vasodilator and beta-adrenoceptor blocking actions, in rabbits.
Pharmacodynamic and pharmacokinetic studies on prizidilol and nipradilol (K-351), antihypertensive drugs with combined vasodilator and beta-adrenoceptor blocking actions, in rabbits.
复制标题
普利地洛和尼普地洛 (K-351) 这两种具有血管扩张和 β-肾上腺素受体阻断作用的抗高血压药物在兔身上的药效学和药代动力学研究。
DOI：
10.1254/jjp.36.519
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
H. Sokabe
中科院分区：
文献类型：
--
作者：
K. Kawashima;T. Watanabe;H. Sokabe
研究了具有血管扩张作用的β肾上腺素受体拮抗剂普齐地洛和尼普拉洛（K-351）对血压正常的清醒兔静脉注射后血压和心率的影响。此外，我们研究了血浆药物浓度与β-肾上腺素受体阻滞活性（通过抑制异丙肾上腺素诱导的心动过速来评估）和血管扩张剂活性（通过抑制血管紧张素II（ANG II）的加压反应来评估）之间的关系。吡齐地洛（4 mg/kg）引起血压显著和持续下降，心率略有增加，而肼苯哒嗪（2 mg/kg）引起相同程度的低血压和明显的心动过速。Nipradilol（1 mg/kg）可显著降低静息心率，但对血压无显著影响。普萘洛尔（1 mg/kg）不影响静息血压和心率。高血压反应ANG II显着衰减只有肼苯哒嗪。异丙肾上腺素诱导的心动过速被普利地洛、尼普拉地洛和普萘洛尔显著抑制。观察到β-肾上腺素受体阻滞活性与血浆药物浓度之间存在良好的相关性。这些数据表明，与肼苯哒嗪相比，吡齐地洛在诱发心动过速方面具有优势，但仍可能引起一定程度的心率增加。Nipradilol具有比普萘洛尔更强的β-肾上腺素受体阻断作用，而其血管扩张作用不明显，至少在家兔中是这样。血浆中普利地洛和尼普拉地洛的浓度是β-肾上腺素受体阻滞活性的良好指标，但不是血管扩张活性的指标。
Effects of prizidilol and nipradilol (K-351), beta-adrenoceptor antagonists with vasodilator action, on blood pressure and heart rate were studied in normotensive conscious rabbits after i.v. administration. In addition, we investigated relationships between plasma drug concentrations and beta-adrenoceptor blocking activity as estimated by the inhibition of isoproterenol-induced tachycardia and vasodilator activity as assessed by the inhibition of pressor response to angiotensin II (ANG II). Prizidilol (4 mg/kg) produced a significant and sustained fall in blood pressure and a slight increase in heart rate, while hydralazine (2 mg/kg) caused the same degree of hypotension and a marked tachycardia. Nipradilol (1 mg/kg) caused a significant reduction of resting heart rate, but had no significant effect on blood pressure. Propranolol (1 mg/kg) did not affect resting blood pressure and heart rate. Hypertensive response to ANG II was significantly attenuated only by hydralazine. Isoproterenol-induced tachycardia was significantly suppressed by prizidilol, nipradilol and propranolol. Good correlations were observed between beta-adrenoceptor blocking activity and plasma drug concentrations. These data suggest that prizidilol has an advantage over hydralazine to induce less tachycardia, but still may cause a certain degree of increase in heart rate. Nipradilol has a more potent beta-adrenoceptor blocking action than propranolol, while its vasodilator action is not obvious, at least in rabbits. Plasma concentrations of prizidilol and nipradilol are good indicators for beta-adrenoceptor blocking activity, but not for vasodilator activity.