Inhibitory effects of 2-[(diethylamino)acetyl]-1,2,3,4-tetrahydro-6, 7-dimethoxyl-1-[1'-(6"-methoxy-2"-naphthalenyl)ethyl]-isoquinoline on isolated guinea pig papillary muscle and heart atrium
Abstract
AIM: To investigate the cardiac actions of 2-[(diethylamino)acetyl]-1,2,3,4-tetrahydro-6, 7-dimethoxyl-1-[1'-(6"-methoxy-2"-naphthalenyl) ethyl]-isoquinoline (CPU57) by comparison with nifedipine and focus on its mechanism of actions.
METHOD: The following were measured and recorded: 1) the rate and contraction of spontaneous beating of the guinea pigs right heart atrium, 2) the isometric tension of the electrically stimulated left heart atrium and the right papillary muscles.
RESULTS: CPU57 had negative inotropic and negative chronotropic actions in isolated heart of guinea pigs as the typical calcium antagonist, nifedipine. However, CPU57 0.01-100 mumol.L(-1) produced less cardiac inhibitory potency than nifedipine and had much stronger negative inotropic action than negative chronotropic action. The decrease in external CaCl2 concentration from 1.5 to 0.3 mmol.L(-1) or increase to 7.5 mmol.L(-1), potentiated or reduced respectively, the inhibitory action of CPU57 on the contraction in paced left heart atrium in normal CaCl2 solution. CPU57 1-10 mumol.L(-1) also inhibited contractile response to CaCl2 in paced left heart atrium with pD2' value of 4.77.
CONCLUSION: CPU57 has calcium antagonism on the heart of guinea pigs.
Keywords:
METHOD: The following were measured and recorded: 1) the rate and contraction of spontaneous beating of the guinea pigs right heart atrium, 2) the isometric tension of the electrically stimulated left heart atrium and the right papillary muscles.
RESULTS: CPU57 had negative inotropic and negative chronotropic actions in isolated heart of guinea pigs as the typical calcium antagonist, nifedipine. However, CPU57 0.01-100 mumol.L(-1) produced less cardiac inhibitory potency than nifedipine and had much stronger negative inotropic action than negative chronotropic action. The decrease in external CaCl2 concentration from 1.5 to 0.3 mmol.L(-1) or increase to 7.5 mmol.L(-1), potentiated or reduced respectively, the inhibitory action of CPU57 on the contraction in paced left heart atrium in normal CaCl2 solution. CPU57 1-10 mumol.L(-1) also inhibited contractile response to CaCl2 in paced left heart atrium with pD2' value of 4.77.
CONCLUSION: CPU57 has calcium antagonism on the heart of guinea pigs.