C-(2-Phenyl-Cyclohexyl)-Methylamine Compounds for the Treatment of Anxiety Disorders

Abstract

Pharmaceutical formulations of [2-(3-methoxyphenyl)-cyclohexylmethyl]-dimethylamine and the metabolites thereof for treating anxiety, anxiety attacks and disorders as well as depression. Related methods of treating anxiety and anxiety attacks or depression are also provided, including methods of administering the active compounds as adjuvants to an antidepressant.

1 . A method for treating anxiety in a mammal, said method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical formulation comprising a C-(2-phenyl-cyclohexyl)-methylamine compound selected from the group consisting of:
 3-(2-dimethylaminomethyl-cyclohexyl)-phenol,   (1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-phenol,   [2-(3-methoxyphenyl)-cyclohexylmethyl]-dimethylamine,   (1R,2R)-[2-(3-methoxyphenyl)-cyclohexylmethyl]-dimethylamine,   sulfuric acid mono-[3-(2-dimethylaminomethyl-cyclohexyl)-phenyl]ester,   sulfuric acid mono-(1R,2R)-[3-(2-dimethylaminomethyl-cyclohexyl)-phenyl]ester,   3-(2-methylaminomethyl-cyclohexyl)-phenol,   (1R,2R)-3-(2-methylaminomethyl-cyclohexyl)-phenol,   3-(2-dimethylaminomethyl-cyclohexyl)-phenol, N-oxide,   (1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-phenol, N-oxide,   6-[3-(2-dimethylaminomethyl-cyclohexyl)-phenoxy]-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid,   6-[(1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-phenoxy]-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid,   4-(2-dimethylaminomethyl-cyclohexyl)-catechol,   (1R,2R)-4-(2-dimethylaminomethyl-cyclohexyl)-catechol,   3-(2-aminomethyl-cyclohexyl)-phenol,   (1R,2R)-3-(2-aminomethyl-cyclohexyl)-phenol,   C-[2-(3-methoxy-phenyl)-cyclohexyl]-methylamine,   (1R,2R)—C-[2-(3-methoxy-phenyl)-cyclohexyl]-methylamine,   [2-(3-methoxy-phenyl)-cyclohexylmethyl]-methylamine,   (1R,2R)-[2-(3-methoxy-phenyl)-cyclohexylmethyl]-methylamine,   [2-(3-methoxy-phenyl)-cyclohexylmethyl]-dimethylamine, N-oxide, and   (1R,2R)-[2-(3-methoxy-phenyl)-cyclohexylmethyl]-dimethylamine, N-oxide,   
     or a physiologically acceptable salt thereof. 
   
   
       2 . A method according to  claim 1 , wherein the pharmaceutical formulation is administered at the first occurrence of an anxiety disorder. 
   
   
       3 . A method for treating anxiety or depression in a mammal, said method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a pharmaceutical formulation comprising a C-(2-phenyl-cyclohexyl)-methylamine compound selected from the group consisting of:
 3-(2-dimethylaminomethyl-cyclohexyl)-phenol,   (1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-phenol,   [2-(3-methoxyphenyl)-cyclohexylmethyl]-dimethylamine,   (1R,2R)-[2-(3-methoxyphenyl)-cyclohexylmethyl]-dimethylamine,   sulfuric acid mono-[3-(2-dimethylaminomethyl-cyclohexyl)-phenyl]ester,   sulfuric acid mono-(1R,2R)-[3-(2-dimethylaminomethyl-cyclohexyl)-phenyl]ester,   3-(2-methylaminomethyl-cyclohexyl)-phenol,   (1R,2R)-3-(2-methylaminomethyl-cyclohexyl)-phenol,   3-(2-dimethylaminomethyl-cyclohexyl)-phenol, N-oxide,   (1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-phenol, N-oxide,   6-[3-(2-dimethylaminomethyl-cyclohexyl)-phenoxy]-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid,   6-[(1R,2R)-3-(2-dimethylaminomethyl-cyclohexyl)-phenoxy]-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid,   4-(2-dimethylaminomethyl-cyclohexyl)-catechol,   (1R,2R)-4-(2-dimethylaminomethyl-cyclohexyl)-catechol,   3-(2-aminomethyl-cyclohexyl)-phenol,   (1R,2R)-3-(2-aminomethyl-cyclohexyl)-phenol,   C-[2-(3-methoxy-phenyl)-cyclohexyl]-methylamine,   (1R,2R)—C-[2-(3-methoxy-phenyl)-cyclohexyl]-methylamine,   [2-(3-methoxy-phenyl)-cyclohexylmethyl]-methylamine,   (1R,2R)-[2-(3-methoxy-phenyl)-cyclohexylmethyl]-methylamine,   [2-(3-methoxy-phenyl)-cyclohexylmethyl]-dimethylamine, N-oxide, and   (1R,2R)-[2-(3-methoxy-phenyl)-cyclohexylmethyl]-dimethylamine, N-oxide,   
     or a physiologically acceptable salt thereof; 
     wherein said C-(2-phenyl-cyclohexyl)-methylamine compound is administered as an adjuvant to at least one antidepressant. 
   
   
       4 . A method as claimed in  claim 1 , wherein said pharmaceutical formulation further comprises a pharmaceutically acceptable carrier or adjuvant. 
   
   
       5 . A method as claimed in  claim 1 , wherein said compound is present in the form of a free base. 
   
   
       6 . A method as claimed in  claim 1 , wherein said compound is present in the form of an isolated enantiomer or diastereoisomer. 
   
   
       7 . A method as claimed in  claim 6 , wherein said compound is present in the form of a 1R,2R enantiomer. 
   
   
       8 . A method as claimed in  claim 1 , wherein said compound is present in the form of a mixture of stereoisomers. 
   
   
       9 . A method as claimed in  claim 8 , wherein said mixture is a racemic mixture.