NEGATIVE CHRONOTROPIC EFFECT OF A NOVEL CLASS-III ANTIARRHYTHMIC DRUG, UK-68,798, DEVOID OF BETA-BLOCKING ACTION ON ISOLATED GUINEA-PIG ATRIA

被引:28
作者
YANG, T [1 ]
TANDE, PM [1 ]
REFSUM, H [1 ]
机构
[1] UNIV TROMSO,INST MED BIOL,DEPT MED PHYSIOL,N-9001 TROMSO,NORWAY
关键词
CLASS-III ANTIARRHYTHMIC; AUTOMATICITY; SINUS NODE; NONCOMPETITIVE ANTAGONISM; IK;
D O I
10.1111/j.1476-5381.1991.tb09804.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 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.
引用
收藏
页码:1417 / 1420
页数:4
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