Article date: May 1993
By: Hui Dong, Jian‐Zhong Sheng, Chi‐Ming Lee, Tak Ming Wong, in Volume 109, Issue 1, pages 113-119
The effects of CPU‐23 (1‐{1‐[(6‐methoxyl)‐naphth‐2‐yl]}‐propyl‐2‐(1‐piperidine)‐acetyl‐6,7‐dimethyoxy‐1,2,3,4‐tetra‐hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone‐anaesthetized rats subjected to coronary artery ligation were also evaluated.
CPU‐23 at 10−6‐10−4m markedly inhibited slow action potential characteristics in guinea‐pig papillary muscles and pace‐maker action potential of rabbit sinoatrial node. It affected fast action potential only at 10−4 M. None of the effects of CPU‐23 was reversed by washout for up to 2 h.
Like nifedipine and diltiazem, CPU‐23 decreased the heart rate of the isolated perfused heart of the rat. However, in contrast to these two classical calcium antagonists which dose‐dependently inhibited the force of contraction, CPU‐23 inhibited and stimulated the force of contraction at 10−7‐3 × 10−6m and 10−5m, respectively.
CPU‐23 at 10−6‐10−5m inhibited the KCl‐induced [Ca2+]i increase in the Ca2+ medium, but did not affect the caffeine‐induced [Ca2+]i increase in the Ca2+‐free medium in isolated ventricular myocytes.
CPU‐23 at 1–5 mg kg−1 reduced dose‐dependently ventricular arrhythmias including ventricular ectopic beats, VT and VF as well as mortality during coronary artery ligation. At 2.5–5 mg kg−1 it even abolished VF, which was accompanied by 100% survival.
It is suggested that CPU‐23 has calcium antagonistic properties in cardiac tissues. It selectively blocks the transmembrane influx of extracellular Ca2+ through Ca2+ channels, thus reducing the heart rate and developed tension, altering the slow action potential characteristics and producing antiarrhythmic effect against ischaemic arrhythmias.
The effects of CPU‐23 (1‐{1‐[(6‐methoxyl)‐naphth‐2‐yl]}‐propyl‐2‐(1‐piperidine)‐acetyl‐6,7‐dimethyoxy‐1,2,3,4‐tetra‐hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone‐anaesthetized rats subjected to coronary artery ligation were also evaluated.
CPU‐23 at 10−6‐10−4m markedly inhibited slow action potential characteristics in guinea‐pig papillary muscles and pace‐maker action potential of rabbit sinoatrial node. It affected fast action potential only at 10−4 M. None of the effects of CPU‐23 was reversed by washout for up to 2 h.
Like nifedipine and diltiazem, CPU‐23 decreased the heart rate of the isolated perfused heart of the rat. However, in contrast to these two classical calcium antagonists which dose‐dependently inhibited the force of contraction, CPU‐23 inhibited and stimulated the force of contraction at 10−7‐3 × 10−6m and 10−5m, respectively.
CPU‐23 at 10−6‐10−5m inhibited the KCl‐induced [Ca2+]i increase in the Ca2+ medium, but did not affect the caffeine‐induced [Ca2+]i increase in the Ca2+‐free medium in isolated ventricular myocytes.
CPU‐23 at 1–5 mg kg−1 reduced dose‐dependently ventricular arrhythmias including ventricular ectopic beats, VT and VF as well as mortality during coronary artery ligation. At 2.5–5 mg kg−1 it even abolished VF, which was accompanied by 100% survival.
It is suggested that CPU‐23 has calcium antagonistic properties in cardiac tissues. It selectively blocks the transmembrane influx of extracellular Ca2+ through Ca2+ channels, thus reducing the heart rate and developed tension, altering the slow action potential characteristics and producing antiarrhythmic effect against ischaemic arrhythmias.
DOI: 10.1111/j.1476-5381.1993.tb13539.x
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