Method for treating neurocognitive dysfunction

Abstract

A method of treating corticosteroid-induced cognitive impairment comprises administering an effective amount of at least one compound of formula I, or pharmaceutically acceptable salts thereof, to a subject in need of such treatment Formula I is: wherein: A is a bridge selected from the following radicals: —(CH 2 ) m —, —CH═CH—, —(CH 2 ) p —O—, —(CH 2 ) p —S—, —(CH 2 ) p —SO 2 —, —(CH 2 ) p —NR 1 — and —SO 2 —NR 2 —, and wherein: m is an integer of from 1 to 3 inclusive; p is an integer selected from 1 and 2; R 1 is selected from the group consisting of hydrogen and C 1 -C 5 alkyl; and R 2 is C 1 -C 5 alkyl; X and Y are independently selected from the group consisting of hydrogen and halogen; R and R′ are independently selected from the group consisting of hydrogen and C 1 -C 5 alkyl; n is an integer from 1 to 12 inclusive; and * denotes an asymmetric carbon.

1 - 18 . (canceled) 
     
     
         19 . A pharmaceutical composition comprising a systemic corticosteroid and a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein: A is a bridge selected from the following radicals: —(CH 2 ) m —, —CH═CH—, —(CH 2 ) p —O—, —(CH 2 ) p —S—, —(CH 2 ) p —SO 2 —, —(CH 2 ) p —NR 1 — and —SO 2 —NR 2 —, and wherein: m is an integer of from 1 to 3 inclusive: p is an integer selected from 1 and 2: R 1  is selected from the group consisting of hydrogen and C 1 -C 5  alkyl; and R 2  is C 1 -C 5  alkyl: X and Y are independently selected from the group consisting of hydrogen and halogen; R and R′ are independently selected from the group consisting of hydrogen and C 1 -C 5  alkyl; n is an integer from 1 to 12 inclusive; and * denotes an asymmetric carbon and the bond designated by the wavy line indicates that the absolute conformation about the asymmetric carbon can be either (R) or (S) only when all four groups attached to the asymmetric carbon are nonequivalent, or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the compound is tianeptine. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein the compound is (R)-tianeptine, substantially free of the corresponding (S)-enantiomer. 
     
     
         22 . The pharmaceutical composition of  claim 19 , wherein the compound is (S)-tianeptine, substantially free of the corresponding (R)-enantiomer. 
     
     
         23 . The pharmaceutical composition of  claim 19 , wherein the systemic corticoid steroid is prednisone.