Bupropion Metabolites and Methods of Their Synthesis and Use

Abstract

Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed.

1 - 126 . (canceled) 
   
   
       127 . A method of treating a disorder ameliorated by the inhibition of neuronal monoamine reuptake, comprising administering to a patient a therapeutically effective amount of a bupropion metabolite, or a pharmaceutically acceptable salt thereof, wherein the disorder is a sexual dysfunction, an affective disorder, a cerebral function disorder, or incontinence. 
   
   
       128 . The method of  claim 127 , wherein the bupropion metabolite is optically pure. 
   
   
       129 . The method of  claim 128 , wherein the optically pure bupropion metabolite is (R,R)-2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl-mopholinol; (S,S)-2-(3-chlorophenyl)-2-hydroxy-3,5,5-trimethyl-mopholinol; (R,R)-2-(tert-butylamino)-1-(3-chlorophenyl)-propan-1-ol; (S,R)-2-(tert-butylamino)-1-(3-chlorophenyl)-propan-1-ol; (S,S)-2-(tert-butylamino)-1-(3-chlorophenyl)-propan-1-ol; (R,S)-2-(tert-butylamino)-1-(3-chlorophenyl)-propan-1-ol; (R)-1-(3-chlorophenyl)-2-[(1,1-dimethylethanol)amino]-1-propanone; or (S)-1-(3-chlorophenyl)-2-[(1,1-dimethylethanol)amino]-1-propanone. 
   
   
       130 . The method of  claim 127 , wherein the bupropion metabolite, or a pharmaceutically acceptable salt thereof, is adjunctively administered with a second pharmacologically active compound. 
   
   
       131 . The method of  claim 130 , wherein the second pharmacologically active compound is a selective serotonin reuptake inhibitor or a 5-HT 3  inhibitor.