Method of slowing ventricular arrhythmias using zatebradine
US5595987A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Jul 22, 1994 |
| Grant date | Jan 21, 1997 |
| Priority date | — |
| Expiry date | Jul 22, 2014 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K31/55
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The present invention relates to a method of using zatebradine by intravenous (IV) injection to retard or eliminate arrhythmias due to abnormal spontaneous activity in subendocardial Purkinje fibers. More specifically, the present invention relates to the use of zatebradine to reduce intracellular Na.sup.+ activity in Purkinje fibers and block I.sub.f current. Arrhythmias due to abnormal spontaneous activity in subendocardial Purkinje fibers occur 24 hours after occlusion of the left anterior descending (LAD) coronary artery in canine heart. These Purkinje fibers in the infarcted hearts are depolarized and have elevated intracellular Na.sup.+ activity. The major current underlying normal automaticity in these fibers is the I.sub.f current. Zatebradine reduces intracellular Na.sup.+ activity in Purkinje fibers by 4 mM. In vivo, 0.25-1.0 mg/kg intravenous injections of zatebradine slow ventricular rhythms by 24%. Although zatebradine also slows sinus nodal rate, it precipitates a more severe arrhythmia. However, during right atrial pacing, capture of ventricular rhythms occurs at lower rates (i.e. 28% reduction) in the presence of zatebradine. Thus, zatebradine eliminates the arrhyth…
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