Compositions and methods for treating or preventing atrial fibrillation

Abstract

The present invention provides compositions and methods for treating or preventing atrial fibrillation (AF). In particular, the present invention provides administration of muscarinic receptor antagonists (e.g., M2-selective muscarinic receptor blockers), administered alone or in combination with other therapeutic agents (e.g., beta-adrenergic receptor blockers) to treat and/or prevent atrial fibrillation.

1 . A method of treating, reversing, and/or preventing cardiac arrhythmia in a subject comprising co-administering to said subject a therapeutically effective amount of a beta-adrenergic receptor blocking agent and a therapeutically effective amount of a muscarinic receptor blocking agent. 
     
     
         2 . The method of  claim 1 , wherein said beta-adrenergic receptor blocking agent is selected from the group consisting of aprenolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, timolol, sotalol, esmolol, cateolol, propranolol, betaxolol, penbutolol, metoprolol, acebutolol, atenolol, metoprolol, pindolol, bisoprolol, nebivolol, amosulalol, landiolol, and tilisolol, including any salts, hydrates, solvates, prodrugs, and any crystal forms in which they may occur. 
     
     
         3 . The method of  claim 1 , wherein said muscarinic receptor blocker is selected from the group comprising atropine, scopolamine, ipratropium, tropicamide, pirenzepine, diphenhydramine, dimenhydrinate, dicyclomine, oxybutynin, tiotropium, cyclopentolate, atropine methonitrate, trihexyphenidyl, tolterodine, solifenacin, darifenacin, benzatropine, and mebeverine, including any salts, hydrates, solvates, prodrugs, and any crystal forms in which they may occur. 
     
     
         4 . The method of  claim 1 , wherein said muscarinic receptor blocker is a M 2 -selective muscarinic receptor subtype. 
     
     
         5 . The method of  claim 1 , wherein said cardiac arrhythmia comprises atrial fibrillation. 
     
     
         6 . The method of  claim 1 , wherein said co-administering of said beta-adrenergic blocker and said muscarinic receptor blocker comprises applying directly to the surface of the heart. 
     
     
         7 . A pharmaceutical composition comprising a therapeutically effective amount of a beta-adrenergic receptor blocker, a therapeutically effective amount of a muscarinic receptor blocker, and a pharmaceutically-acceptable carrier. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein said beta-adrenergic receptor blocker is selected from the group comprising aprenolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, timolol, sotalol, esmolol, cateolol, propranolol, betaxolol, penbutolol, metoprolol, acebutolol, atenolol, metoprolol, pindolol, bisoprolol, nebivolol, amosulalol, landiolol, and tilisolol, including any salts, hydrates, solvates, prodrugs, and any crystal forms in which they may occur. 
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein said muscarinic receptor blocker is selected from the group comprising atropine, scopolamine, ipratropium, tropicamide, pirenzepine, diphenhydramine, dimenhydrinate, dicyclomine, oxybutynin, tiotropium, cyclopentolate, atropine methonitrate, trihexyphenidyl, tolterodine, solifenacin, darifenacin, benzatropine, and mebeverine, including any salts, hydrates, solvates, prodrugs, and any crystal forms in which they may occur. 
     
     
         10 - 12 . (canceled) 
     
     
         13 . A method of treating, reversing, and/or preventing cardiac arrhythmia in a subject comprising administering to said subject a therapeutically effective amount of an M 2 -selective muscarinic receptor blocking agent. 
     
     
         14 . The method of  claim 13 , wherein the cardiac arrhythmia is atrial fibrillation. 
     
     
         15 . The method of  claim 13 , wherein said M 2 -selective muscarinic receptor blocking agent selectively blocks the M 2  receptor subtype by at least five-fold versus the M 3  receptor subtype. 
     
     
         16 . The method of  claim 15 , wherein said M 2 -selective muscarinic receptor blocking agent selectively blocks the M 2  receptor subtype by at least five-fold versus the M 1  receptor subtype. 
     
     
         17 . The method of  claim 1 , wherein said M 2 -selective muscarinic receptor blocking agent is selected from Sch 211803, TD-6301, and methoctramine. 
     
     
         18 - 20 . (canceled)