ANTIARRHYTHMIC ACTIVITY OF 1-(7-INDENYLOXY)-3-ISOPROPYLAMINOPROPANE-2-OL HYDROCHLORIDE (YB-2) AND ITS OPTICAL ISOMERS

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The antiarrhythmic activities of YB-2 and its optical isomers were investigated in experimentally induced arrhythmias in anesthetized guinea pigs and dogs, and compared with those of propranolol. The local anesthetic and negative inotropic properties of these agents were also examined because of their possible contribution to the antiarrhythmic profile. In anesthetized guinea pigs, these agents showed a significant protecting effect against ouabain-induced arrhythmias; tile order of the potency was as follows, 1-YB-2=dl-YB-2>propranolol>d-YB-2. The similar tendency was also observed in anesthetized dogs. YB-2 and its 1-isomer, 0.1-0.4 mg/kg i.v., were equipotent with propranolol with respect to their protecting effects against methylchloroform-epinephrine-induced ventricular fibrillation in dogs, while the d-isomer, 4 mg/kg i.v., failed to inhibit the arrhythmias. YB-2 and its optical isomers and propranolol were found to have significant local anesthetic activities in guinea pig cornea and dorsal skin and negative inotropic activities in isolated guinea pig atria. There was no significant difference among these agents in each activity. The results suggest that YB-2 and its optical isomers appear to have a similar potency ratio for antiarrhythmic activity as is the case with propranolol and its optical isomers, and that YB-2 may prove to be a useful antiarrhythmic agent in clinical situations.
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