Methods for treating or preventing fatigue

1. A method for treating or preventing fatigue in a subject, comprising administering to a subject in need thereof, a treatment or prevention effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

R x is a member selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, halogen selected from F, Cl, Br and I, alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy containing 1 to 3 carbon atoms;

x is an integer of 1 to 3, with the proviso that R may be the same or different when x is 2 or 3;

R 1 and R 2 can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, aryl, heteroaryl, arylalkyl, and cycloalkyl of 3 to 7 carbon atoms;

or R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle substituted with a member selected from the group consisting of hydrogen, alkyl, aryl, and heteroaryl groups, wherein the cyclic compound can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom; and

an additional agent or treatment.

2. The method of claim 1 , wherein R is hydrogen and x=1.

3. The method of claim 1 , wherein R, R 1 , and R 2 are all hydrogen and x=1.

4. The method of claim 1 , wherein the compound of Formula I is:

or a pharmaceutically acceptable salt, ester, or prodrug thereof.

5. The method of claim 1 , wherein the compound of Formula I is an enantiomer substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of the compound predominates.

6. The method of claim 5 , wherein one enantiomer predominates to the extent of at least about 90%.

7. The method of claim 5 , wherein one enantiomer predominates to the extent of at least about 98%.

8. The method of claim 5 , wherein the compound is

or a pharmaceutically acceptable salt, ester, or prodrug thereof.

9. The method of claim 1 , wherein the fatigue is associated with a disease, disorder or condition.

10. The method of claim 9 , wherein the disease, disorder or condition is selected from the group consisting of depression, cancer, multiple sclerosis, Parkinson's disease, Alzheimer's disease, chronic fatigue syndrome, fibromyalgia, chronic pain, traumatic brain injury, AIDS, and osteoarthritis.

11. The method of claim 1 , wherein the fatigue is associated with a treatment or medication.

12. The method of claim 11 , wherein the treatment or medication is selected from the group consisting of chemotherapy, radiation therapy, bone marrow transplant, and anti-depressant treatment.

13. The method of claim 1 , wherein the compound is administered prior to an event that may result in fatigue, concurrently with an event that may result in fatigue, and/or after the onset of fatigue.

14. The method of claim 1 , wherein the treatment or prevention effective amount of the compound is from about 0.01 mg/kg/dose to about 300 mg/kg/dose.

15. A method for treating or preventing fatigue in a subject, comprising orally administering to a subject in need thereof, a treatment or prevention effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

R x is a member selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, halogen selected from F, Cl, Br and I, alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy containing 1 to 3 carbon atoms;

x is an integer of 1 to 3, with the proviso that R may be the same or different when x is 2 or 3;

R 1 and R 2 can be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, aryl, heteroaryl, arylalkyl, and cycloalkyl of 3 to 7 carbon atoms;

or R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle substituted with a member selected from the group consisting of hydrogen, alkyl, aryl, and heteroaryl groups, wherein the cyclic compound can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom.

16. The method of claim 15 , wherein R is hydrogen and x=1.

17. The method of claim 15 , wherein R, R 1 , and R 2 are all hydrogen and x=1.

18. The method of claim 15 , wherein the compound of Formula I is:

or a pharmaceutically acceptable salt, ester, or prodrug thereof.

19. The method of claim 15 , wherein the compound of Formula I is an enantiomer substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of the compound predominates.

20. The method of claim 19 , wherein one enantiomer predominates to the extent of at least about 90%.

21. The method of claim 19 , wherein one enantiomer predominates to the extent of at least about 98%.

22. The method of claim 19 , wherein the compound is

or a pharmaceutically acceptable salt, ester, or prodrug thereof.

23. The method of claim 15 , wherein the fatigue is associated with a disease, disorder or condition.

24. The method of claim 23 , wherein the disease, disorder or condition is selected from the group consisting of depression, cancer, multiple sclerosis, Parkinson's disease, Alzheimer's disease, chronic fatigue syndrome, fibromyalgia, chronic pain, traumatic brain injury, AIDS, and osteoarthritis.

25. The method of claim 15 , wherein the fatigue is associated with a treatment or medication.

26. The method of claim 25 , wherein the treatment or medication is selected from the group consisting of chemotherapy, radiation therapy, bone marrow transplant, and anti-depressant treatment.

27. The method of claim 15 , wherein the compound is administered prior to an event that may result in fatigue, concurrently with an event that may result in fatigue, and/or after the onset of fatigue.

28. The method of claim 15 , wherein the treatment or prevention effective amount of the compound is from about 0.01 mg/kg/dose to about 300 mg/kg/dose.