Use of derivatives of valproic acid and 2-valproenic acid amides for the treatment of mania in bipolar disorder

Abstract

A method for the treatment of mania in bipolar disorder using derivatives of valproic acid and 2-valproenic acid amides having the following structures: wherein R 1 , R 2 , and R 3 are independently the same or different and are hydrogen, a C 1 -C 6 alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, or a compound containing a valproic or a 2-valproenic moiety, as well as pharmaceutical compositions comprising these derivatives or compounds.

What is claimed:  
     
         1 . A method of treating bipolar disorder in a subject comprising administering to the subject a therapeutically effective amount of a derivative of a valproic acid amide or a 2-valproenic acid amide having one of the following structures:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , and R 3  are independently the same or different and are hydrogen, a C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, to thereby treat the bipolar disorder.  
     
     
         2 . The method of  claim 1 , wherein the derivative has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein the derivative is in a pharmaceutical composition with a pharmaceutically acceptable carrier.  
     
     
         4 . The method of  claim 1 , wherein the derivative is in the form of a pharmaceutically acceptable salt.  
     
     
         5 . The method of  claim 1 , wherein the bipolar disorder is mania.  
     
     
         6 . The method of  claim 1 , wherein the subject is human.  
     
     
         7 . The method of  claim 1 , wherein the route of administration is selected from the group consisting of oral, parenteral, intraperitoneal, intravenous, intramuscular, transdermal, subcutaneous, topical and rectal administration.  
     
     
         8 . The method of  claim 1 , wherein the effective amount is an amount from about 10 mg to 1,000 mg.  
     
     
         9 . The method of  claim 8 , wherein the effective amount is an amount from about 50 mg to 500 mg.  
     
     
         10 . The method of  claim 1 , wherein the derivative has structure I and the C 1 -C 6  alkyl group is a linear chain alkyl group.  
     
     
         11 . The method of  claim 1 , wherein the derivative has structure I and the C 1 -C 6  alkyl group is a branched chain alkyl group.  
     
     
         12 . The method of  claim 1 , wherein the derivative has structure I and the aralkyl group is selected from the group consisting of a benzyl, alkylbenzyl, hydroxybenzyl, alkoxycarbonylbenzyl, aryloxycarbonylbenzyl, carboxybenzyl, nitrobenzyl, cyanobenzyl, and halobenzyl group.  
     
     
         13 . The method of  claim 1 , wherein the derivative has structure I and the aryl group is selected from the group consisting of a phenyl, naphthyl, anthracenyl, pyridinyl, indolyl, furanyl, alkylphenyl, hydroxyphenyl, alkoxycarbonylphenyl, aryloxycarbonylphenyl, nitrophenyl, cyanophenyl, halophenyl group, mercaptophenyl, and aminophenyl group.  
     
     
         14 . The method of  claim 1 , wherein the derivative has structure II and the C 1 -C 6  alkyl group is a linear chain alkyl group.  
     
     
         15 . The method of  claim 1 , wherein the derivative has structure II and the C 1 -C 6  alkyl group is a branched chain alkyl group.  
     
     
         16 . The method of  claim 1 , wherein the derivative has structure II and the aralkyl group is selected from the group consisting of a benzyl, alkylbenzyl, hydroxybenzyl, alkoxycarbonylbenzyl, aryloxycarbonylbenzyl, carboxybenzyl, nitrobenzyl, cyanobenzyl, and halobenzyl group.  
     
     
         17 . The method of  claim 1 , wherein the derivative has structure II and the aryl group is selected from the group consisting of a phenyl, naphthyl, anthracenyl, pyridinyl, indolyl, furanyl, alkylphenyl, hydroxyphenyl, alkoxycarbonylphenyl, aryloxycarbonylphenyl, nitrophenyl, cyanophenyl, halophenyl group, mercaptophenyl, and aminophenyl group.