Koe 3290在正常受试者中的β-肾上腺素能受体阻断活性及心脏选择性评估。

The assessment of the beta-adrenoceptor blocking activity and cardioselectivity of Koe 3290 in normal subjects.

Pringle T H, McNeill A J, Riddell J G, Shanks R G

Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.

Br J Clin Pharmacol. 1987 Nov;24(5):581-9. doi: 10.1111/j.1365-2125.1987.tb03216.x.

Abstract

The beta-adrenoceptor antagonist activity, cardioselectivity and antilipolytic properties of Koe 3290 were investigated in healthy subjects. 2. Koe 3290 12.5, 25, 50 and 100 mg, atenolol 25, 50 and 100 mg and placebo were given in double-blind randomised order to eight subjects. All doses of both Koe 3290 and atenolol reduced supine, standing and exercise heart rate (P less than 0.02). From 2 to 8 h after administration the exercise heart rate after Koe 3290 100 mg was similar to that for atenolol 50 mg. 3. The cardioselectivity of Koe 3290 and atenolol was compared. Koe 3290 50, 100 and 150 mg, atenolol 50 and 100 mg and placebo were given to six subjects in a double-blind random order. Isoprenaline dose-response curves were constructed for cardiovascular parameters and finger tremor. 4. For doses which were equipotent at the beta 1-adrenoceptor (Koe 3290 100 mg and atenolol 50 mg) atenolol caused less attenuation of heart rate, diastolic blood pressure, forearm blood flow and finger tremor (P less than 0.02). 5. There was no difference in the isoprenaline-induced changes in serum free fatty acids, blood glucose, plasma lactate or potassium after Koe 3290 and atenolol. Koe 3290 attenuated the rise in serum insulin more than atenolol (P less than 0.02). 6. Koe 3290 is an effective beta-adrenoceptor blocking drug in man. It is not as cardioselective as atenolol and does not possess specific antilipolytic properties.

摘要

在健康受试者中研究了Koe 3290的β-肾上腺素能受体拮抗活性、心脏选择性和抗脂解特性。2. 将Koe 3290 12.5毫克、25毫克、50毫克和100毫克、阿替洛尔25毫克、50毫克和100毫克以及安慰剂以双盲随机顺序给予8名受试者。Koe 3290和阿替洛尔的所有剂量均降低了仰卧位、站立位和运动时的心率（P<0.02）。给药后2至8小时，Koe 3290 100毫克后的运动心率与阿替洛尔50毫克后的相似。3. 比较了Koe 3290和阿替洛尔的心脏选择性。将Koe 3290 50毫克、100毫克和150毫克、阿替洛尔50毫克和100毫克以及安慰剂以双盲随机顺序给予6名受试者。构建了异丙肾上腺素对心血管参数和手指震颤的剂量反应曲线。4. 对于在β1-肾上腺素能受体处等效的剂量（Koe 3290 100毫克和阿替洛尔50毫克），阿替洛尔引起的心率、舒张压、前臂血流量和手指震颤的衰减较小（P<0.02）。5. Koe 3290和阿替洛尔后，异丙肾上腺素诱导的血清游离脂肪酸、血糖、血浆乳酸或钾的变化没有差异。Koe 3290比阿替洛尔更能减弱血清胰岛素的升高（P<0.02）。6. Koe 3290是一种对人体有效的β-肾上腺素能阻断药物。它的心脏选择性不如阿替洛尔，也不具有特定的抗脂解特性。