新型III类抗心律失常药物UK-68,798对离体豚鼠心房无β受体阻滞作用，但具有负性变时效应。
Negative chronotropic effect of a novel class III antiarrhythmic drug, UK-68,798, devoid of beta-blocking action on isolated guinea-pig atria.
作者信息
Yang T, Tande P M, Refsum H
机构信息
Department of Medical Physiology, University of Tromsø, Norway.
出版信息
Br J Pharmacol. 1991 Jun;103(2):1417-20. doi: 10.1111/j.1476-5381.1991.tb09804.x.
Abstract
- The chronotropic effects of a novel class III antiarrhythmic drug, UK-68,798, and the beta-adrenoceptor blocker, propranolol, for comparison, were studied on spontaneously beating right atria isolated from guinea-pigs in the absence and presence of increasing concentrations of isoprenaline (10(-10)-10(-4) M). 2. UK-68,798 (10(-9)-10(-5) M) decreased spontaneous atrial rate by 6-21%. Propranolol (10(-8) -10(-6) M) also had a negative but significantly smaller chronotropic effect. 3. UK-68,798 dose-dependently reduced the maximal positive chronotropic effect induced by isoprenaline, but without significantly shifting the concentration-response curve for isoprenaline in a parallel fashion. A pD'2 value of 5.88 was obtained. As expected, propranolol displayed a competitive inhibition with a pA2 value of 8.21. 4. The results demonstrate a negative chronotropic effect of UK-68,798, which is not associated with a beta-adrenoceptor blocking action. We suggest that the negative chronotropic effect is linked with potassium channel blockade and thereby the class III antiarrhythmic action of UK-68,798.
摘要
- 为作比较，研究了新型III类抗心律失常药物UK-68,798和β-肾上腺素能受体阻滞剂普萘洛尔对从豚鼠分离出的自主搏动右心房的变时作用，实验分别在不存在和存在递增浓度的异丙肾上腺素（10⁻¹⁰ - 10⁻⁴ M）的情况下进行。2. UK-68,798（10⁻⁹ - 10⁻⁵ M）使心房自发率降低了6 - 21%。普萘洛尔（10⁻⁸ - 10⁻⁶ M）也有负性变时作用，但明显较小。3. UK-68,798剂量依赖性地降低了异丙肾上腺素诱导的最大正性变时作用，但未使异丙肾上腺素的浓度-反应曲线发生明显的平行位移。获得的pD'2值为5.88。正如预期的那样，普萘洛尔表现出竞争性抑制作用，pA2值为8.21。4. 结果表明UK-68,798具有负性变时作用，这与β-肾上腺素能受体阻断作用无关。我们认为这种负性变时作用与钾通道阻滞有关，从而与UK-68,798的III类抗心律失常作用相关。
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