Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-07-22
1997-01-21
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514821, A61K 3155
Patent
active
055959873
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 arrhythmia when the right atria is paced at the original sinus rate.
REFERENCES:
patent: 4490369 (1984-12-01), Reiffen et al.
CA 120:182730q, Goethals et al., 1993.
CA 120:235793w, Bril et al., May 9, 1994.
Klein Richard
Lasker Steven
Jordan Kimberly
The Trustees of Columbia University in the City of New York
White John P.
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