Why the study?
Does CRD-401 reduce experimentally induced arrhythmias in guinea-pigs and dogs compared to quinidine and propranolol?
Does CRD-401 reduce experimentally induced arrhythmias in guinea-pigs and dogs compared to quinidine and propranolol?
CRD-401 demonstrates antiarrhythmic properties with a longer duration of action than propranolol in epinephrine-induced arrhythmias and exhibits non-competitive beta-blocking activity in preclinical models.
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Animal data on CRD-401 should not change practice; leaves open translation to human arrhythmia trials.
The effect of CRD-401 on several types of experimentally induced arrhythmias in guinea-pigs and dogs and the antagonistic effect against isoproterenol in the isolated atrium of guinea-pig were studied and compared with quinidine and propranolol. In epinephrine-induced arrhythmias of guinea-pigs, propranolol had a notable but brief depressive effect, which was observed only 5 min after administration of the drug. Although the potency of CRD-401 was weaker than that of propranolol in these arrhythmias, the effect persisted for more than 35 min after administration. In ouabain-induced arrhythmias of guinea-pigs, CRD-401 and propranolol showed similar depressive effects. Quinidine had little effect on both epinephrine- and ouabain-induced arrhythmias. Both CRD-401 and propranolol failed to reverse the arrhythmias produced by two-stage coronary artery ligation. Propranolol showed a competitive antagonism against the positive chronotropic effect of isoproterenol, while CRD-401 revealed a non-competitive β-blocking action. Quinidine produced no blocking effect in the present experiments.
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Yamada et al. (1973) studied this question.
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