Methods of treating neurological and other disorders using enantiopure deuterium-enriched bupropion

Abstract

The invention provides enantiopure deuterium-enriched bupropion, pharmaceutical compositions, and methods of treating neurological disorders, movement disorders, cardiovascular disorders, metabolic disorders, and other disorders using enantiopure deuterium-enriched bupropion. A preferred aspect of the invention provides methods of treating obesity and sexual dysfunction using enantiopure deuterium-enriched bupropion.

1 - 35 . (canceled) 
     
     
         36 . A method of treating a disorder selected from the group consisting of seasonal affective disorder, and treatment-resistant depression, comprising administering to a patient in need thereof a therapeutically effective amount of a deuterium-enriched compound of Formula II having an optical purity of at least 75% enantiomeric excess to treat the disorder, wherein Formula II is represented by: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         A 1 , A 2 , A 3 , and A 4  are independently —C(R 6 )(R 7 )(R 8 ); 
         R 1 , R 2 , R 3 , R 4 , and R 5  are independently H or D; 
         R 6 , R 7 , and R 8  each represent independently for each occurrence H or D; and 
         Z is H or D, provided that the abundance of deuterium in Z is at least 30%. 
       
     
     
         37 . The method of  claim 36 , wherein the disorder is seasonal affective disorder. 
     
     
         38 - 43 . (canceled) 
     
     
         44 . The method of  claim 36 , wherein R 1 , R 2 , R 3 , R 4 , and R 5  are H. 
     
     
         45 . The method of  claim 36 , wherein A 1 , A 2 , A 3 , and A 4  are —CH 3 . 
     
     
         46 . The method of  claim 36 , wherein the compound is a compound of Formula II-A having an optical purity of at least 75% enantiomeric excess, wherein Formula II-A is represented by: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein Z is H or D, provided that the abundance of deuterium in Z is at least 30%. 
       
     
     
         47 . The method of  claim 36 , wherein the abundance of deuterium in Z is at least 60%. 
     
     
         48 . The method of  claim 36 , wherein the abundance of deuterium in Z is at least 75%. 
     
     
         49 . The method of  claim 36 , wherein the abundance of deuterium in Z is at least 90%. 
     
     
         50 . The method of  claim 36 , wherein the compound has an enantiomeric excess of at least 85%. 
     
     
         51 . The method of  claim 36 , wherein the compound has an enantiomeric excess of at least 90%. 
     
     
         52 . The method of  claim 36 , wherein the compound has an enantiomeric excess of at least 95%. 
     
     
         53 . The method of  claim 36 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, each having an optical purity of at least 90% enantiomeric excess. 
       
     
     
         54 . The method of  claim 36 , wherein the compound is: 
       
         
           
           
               
               
           
         
         having an optical purity of at least 90% enantiomeric excess. 
       
     
     
         55 - 59 . (canceled) 
     
     
         60 . The method of  claim 36 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, each having an optical purity of at least 95% enantiomeric excess. 
       
     
     
         61 . The method of  claim 36 , wherein the compound is: 
       
         
           
           
               
               
           
         
         having an optical purity of at least 95% enantiomeric excess. 
       
     
     
         62 . The method of  claim 36 , wherein the compound is administered at a daily dose in the range of about 50 mg to 75 mg, 75 mg to 100 mg, 100 mg to 125 mg, 125 mg to 150 mg, 150 mg to 175 mg, 175 mg to 200 mg, 200 mg to 225 mg, 225 mg to 250 mg, 250 mg to 275 mg, or 275 mg to 300 mg. 
     
     
         63 . The method of  claim 36 , wherein the compound is administered at a daily dose in the range of about 50 mg to 175 mg, about 175 mg to 200 mg, or about 200 mg to 225 mg. 
     
     
         64 . The method of  claim 36 , wherein the disease is treatment-resistant depression.