Method for treating neurocognitive dysfunction

• US 20090275541A1
• Filed: 05/05/2008
• Published: 11/05/2009
• Est. Priority Date: 05/05/2008
• Status: Active Grant

• Current Assignee: Tonix pharma holdings limited (Tonix Pharmaceuticals Holding Corp.)
• Original Assignee: Tonix pharma holdings limited (Tonix Pharmaceuticals Holding Corp.)
• Inventors: Sullivan, Gregory M.
• Granted Patent: US 9,314,469 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

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: —(CH₂)_m—, —CH═CH—, —(CH₂)_p—O—, —(CH₂)_p—S—, —(CH₂)_p—SO₂—, —(CH₂)_p—NR₁— and —SO₂—NR₂—, and wherein: m is an integer of from 1 to 3 inclusive; p is an integer selected from 1 and 2; R₁ is selected from the group consisting of hydrogen and C₁-C₅ alkyl; and R₂ is C₁-C₅ 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 C₁-C₅ alkyl; n is an integer from 1 to 12 inclusive; and * denotes an asymmetric carbon.

Claims

1. A method of treating the neurocognitive side effects associated with corticosteroid treatment as a result of a condition in a subject in need of such treatment, comprising administering to the subject an effective amount of at least one compound of formula I

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

SO₂—

NR₂—

.

3. The method according to claim 2, wherein R and R′

are hydrogen.

4. The method of claim 1, wherein the compound of formula I is tianeptine or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the compound is (R)-tianeptine, substantially free of the corresponding (S)-enantiomer.

6. The method of claim 4, wherein the compound is (S)-tianeptine, substantially free of the corresponding (R)-enantiomer.

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

8. 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 600 mg/day.

9. 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 10 to about 400 mg/day.

10. The method of claim 1, wherein the effective amount of the at least one compound of formula I administered to the subject is about 25 to about 300 mg/day.

11. The method of claim 1, wherein the at least one compound of formula I is administered to the subject as a pharmaceutical composition.

12. The method of claim 11, wherein the condition is pulmonary condition.

13. The method of claim 12, wherein the pulmonary condition is selected from the group consisting of asthma, chronic obstructive pulmonary disease and pulmonary sarcoidosis.

14. The method of claim 11, wherein the condition is selected from the group consisting of a cardiac condition, a gastrointestinal condition, a rheumatic condition, a collagen-vascular or dermatological condition, a renal condition, an endocrine condition.

15. The method of claim 14, wherein the condition is pericarditis, hepatitis, ulcerative colitis or Crohn'"'"'s disease, rheumatoid arthritis or psoriatic arthritis, polymyositis, polyarteritis nodosa, vasculitis, systemic dermatomyositis, eczema, cutaneous sarcoidosis, mycosis fungoides, severe seborrheic dermatitis, psoriasis, and systemic lupus erythematosus, nephritic syndrome, or lupus nephritis, a hyperthyroid state or hypercalcemia associated with malignancy and sarcoidosis.

16. The method of claim 11, wherein the condition is the prophylaxis of the rejection of a transplanted organ.

17. The method of claim 1, wherein the compound of formula I is administered with a systemic corticosteroid.

18. The method of claim 17, wherein the systemic corticosteroid is prednisone.

19. A pharmaceutical composition comprising a systemic corticosteroid and a compound of formula I.

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 corticosteroid is prednisone.