Treatment of congestive heart failure

Abstract

Combinations of diuretics and vasopressin antagonists are useful to slow and reverse the symptoms and process of congestive heart failure, to increase the excretion of water in the urine, and to decrease the excretion of sodium and potassium ions in urine. Preferred vasopressin antagonists have the formula wherein R and R 5 are hydrogen or lower alkyl; R 1 , R 2 , and R 3 are hydrogen, halo, alkyl, alkoxy, and amino; and R 4 is hydrogen or phenyl, and a pharmaceutically acceptable salt thereof.

What is claimed is:  
     
         1 . A pharmaceutical composition comprising an effective amount of a diuretic agent and an effective amount of a vasopressin antagonist.  
     
     
         2 . A composition according to  claim 1  employing a loop diuretic agent.  
     
     
         3 . A composition according to  claim 1  employing a vasopressin antagonist of Formula I  
       
         
           
           
               
               
           
         
         wherein R and R 5  are hydrogen or lower alkyl:  
         R 1 , R 2 , and R 3  independently are hydrogen, halo, lower alkyl, lower alkoxy, amino, alkylamino, or dialkylamino; and R 4  is hydrogen, phenyl or substituted phenyl, and pharmaceutically acceptable salts thereof.  
       
     
     
         4 . A composition according to  claim 3  in which the vasopressin antagonist is conivaptan.  
     
     
         5 . A composition to  claim 2  employing furosemide.  
     
     
         6 . A composition to  claim 5  employing the vasopressin antagonist conivaptan.  
     
     
         7 . A method for preventing and treating congestive heart failure and other edematous conditions in a mammal comprising administering an effective amount of a combination of at least one diuretic agent and at least one vasopressin antagonist.  
     
     
         8 . A method according to  claim 7  wherein furosemide is administered in combination with conivaptan.  
     
     
         9 . A method for inhibiting excretion of sodium ions in the urine of an animal comprising administering to the animal an effective amount of a diuretic in combination with a vasopressin antagonist.  
     
     
         10 . A method according to  claim 9  wherein the diuretic administered is a loop diuretic.  
     
     
         11 . A method according to  claim 10  wherein furosemide is administered in combination with conivaptan.  
     
     
         12 . A method for inhibiting the excretion of potassium ions in the urine of an animal comprising administering to the animal an effective amount of a diuretic in combination with a vasopressin antagonist.  
     
     
         13 . A method according to  claim 12  wherein the diuretic is a loop diuretic.  
     
     
         14 . A method according to  claim 13  wherein furosemide is administered in combination with conivaptan.  
     
     
         15 . A method for treating edematous states in an animal comprising administering an effective amount of a diuretic agent in combination with a vasopressin antagonist.