Compositions and methods for treatment of neuropathic pain, fibromyalgia and chronic fatigue syndrome

1 . A method of treating a disorder selected from the group consisting of neuropathic pain, fibromyalgia and chronic fatigue syndrome in a subject in need of such treatment, comprising administering to the subject an effective amount of at least one compound of Formula I:

wherein:

A is diradical selected from the group consisting of —(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 —; wherein:

m is 1, 2 or 3;

p is 1 or 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 halogen;

j and k are integers independently selected from the group consisting of 0, 1 and 2;

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 indicates that the absolute conformation about the asymmetric carbon may be either (R) or (S) when all four groups attached to the asymmetric carbon are nonequivalent.

2 . A method of treating a disorder selected from the group consisting of neuropathic pain, fibromyalgia and chronic fatigue syndrome in a subject in need of such treatment, comprising administering to the subject an effective amount of at least one compound of Formula I:

wherein:

A is diradical selected from the group consisting of —(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 —; wherein:

m is 1, 2 or 3;

p is 1 or 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 halogen;

j and k are integers independently selected from the group consisting of 0 and 1;

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 indicates that the absolute conformation about the asymmetric carbon may be either (R) or (S) when all four groups attached to the asymmetric carbon are nonequivalent.

3 . A method of treating a disorder selected from the group consisting of neuropathic pain, fibromyalgia and chronic fatigue syndrome in a subject in need of such treatment, comprising administering to the subject an effective amount of at least one compound of Formula I:

wherein:

A is diradical selected from the group consisting of —(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 —; wherein:

m is 1, 2 or 3;

p is 1 or 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 halogen;

j and k are integers independently selected from the group consisting of 0 and 1;

R and R′ are independently selected from the group consisting of hydrogen and C 1 -C 5 alkyl;

n is an integer from 4 to 8 inclusive; and

* denotes an asymmetric carbon and the bond designated by indicates that the absolute conformation about the asymmetric carbon may be either (R) or (S) when all four groups attached to the asymmetric carbon are nonequivalent.

4 . The method according to claim 1 , wherein A is —SO 2 NR 2 —.

5 . The method according to claim 4 , wherein j and k are 0.

6 . The method of claim 5 , wherein the compound of Formula I is tianeptine or a pharmaceutically acceptable salt thereof.

7 . The method of claim 6 , wherein the compound is (R)-tianeptine, substantially free of the corresponding (S)-enantiomer.

8 . The method of claim 6 , wherein the compound is (S)-tianeptine, substantially free of the corresponding (R)-enantiomer.

9 . The method of claim 1 , wherein the subject is a human.

10 . The method of claim 1 , wherein the effective amount of the at least one compound of Formula I administered to the subject is from about 2 to about 100 mg per day.

11 . The method of claim 1 , wherein the effective amount of the at least one compound of Formula I administered to the subject is from about 5 to about 60 mg per day.

12 . The method of claim 1 , wherein the effective amount of the at least one compound of Formula I administered to the subject is about 30 mg per day.

13 . The method of claim 1 , wherein the at least one compound of Formula I is administered by an enteral administration route.

14 . The method of claim 1 , wherein the at least one compound of Formula I is administered by a parenteral administration route.

15 . The method of claim 1 , wherein the parenteral administration route is selected from the group consisting of intravenous, intramuscular, intraarterial, intraperitoneal, intravaginal, intravesical, intradermal, topical, subcutaneous, and instillation into the body of the subject.

16 . The method of claim 1 , wherein the disorder is neuropathic pain.

17 . The method of claim 1 , wherein the disorder is fibromyalgia.

18 . The method of claim 1 , wherein the disorder is chronic fatigue syndrome.

19 . The method of claim 1 , wherein the at least one compound of Formula I administered to the subject is contained in a pharmaceutical composition.

20 . The method of claim 19 , wherein the pharmaceutical composition comprises a controlled-release pharmaceutical composition.