Methods for treating neuropsychiatric disorders

• US 6,974,821 B2
• Filed: 09/23/2003
• Issued: 12/13/2005
• Est. Priority Date: 04/14/1998
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Coyle, Joseph, Tsai, Guochuan
• Primary Examiner(s): Henley, III, Raymond J.
• Application Number:
  US10/668,583
• Publication Number:
  US 20040092530A1
• Time in Patent Office: 812 Days
• Field of Search: 514/380, 514/297, 514/319
• US Class Current: 514/297
• 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 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/315 Zinc compounds
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• 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

Abstract

The invention provides methods for treating neuropsychiatric disorders such as schizophrenia, Alzheimer'"'"'s Disease, autism, depression, benign forgetfulness, childhood learning disorders, closed head injury, and attention deficit disorder. The methods entail administering to a patient diagnosed as having a neuropsychiatric disorder a pharmaceutical composition containing (i) a therapeutically effective amount of D-alanine (or a modified form thereof), provided that the composition is substantially free of D-cycloserine, and/or (ii) D-serine (or a modified form thereof), and/or (iii) 105 to 500 mg of D-cycloserine (or a modified form thereof), and/or (iv) N-methylglycine (or a modified form thereof).

Claims

1. A method for treating autism, the method comprising administering to a patient diagnosed as suffering from autism a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of D-cycloserine, a salt of D-cycloserine, an ester of D-cycloserine, an alkylated D-cycloserine and a precursor of D-cycloserine.

2. The method according to claim 1, wherein the compound is D-cycloserine.

3. The method of claim 1, wherein the compound is a salt of D-cycloserine selected from the group consisting of a sodium salt, a potassium salt, a calcium salt, a magnesium salt, a zinc salt, and an ammonium salt of D-cycloserine.

4. The method of claim 1, wherein the compound is an ester of D-cycloserine having an ester group with 1-20 carbon atoms.

5. The method of claim 1, wherein the compound is an alkylated D-cycloserine having an alkyl group with 1-20 carbon atoms.

6. The method of claim 1, wherein the compound is a precursor of D-cycloserine.

7. The method of claim 1, wherein the pharmaceutical composition is administered to the patient for at least one week.

8. The method of claim 1, wherein the pharmaceutical composition is administered to the patient for at least 4 weeks.

9. The method of claim 1, wherein the pharmaceutical composition is administered to the patient for at least 6 weeks.

10. The method of claim 1, wherein the pharmaceutical composition is administered to the patient for at least 8 weeks.

11. The method of claim 1, wherein the pharmaceutical composition is administered to the patient at least once daily.

12. The method of claim 1, wherein the pharmaceutical composition is administered to the patient in two doses per day.

13. The method of claim 1, wherein the pharmaceutical composition is administered to the patient in three doses per day.

14. The method of claim 1, wherein the pharmaceutical composition is administered to the patient in four doses per day.

15. The method of claim 1, wherein the pharmaceutical composition is administered by a route selected from the group consisting of oral, intravenous, trans-mucosal, pulmonary, transdermal, ocular, buccal, sublingual, intraperitoneal, intrathecal, and intramuscular routes.

16. The method of claim 15, wherein the pharmaceutical composition is administered by an oral route.

17. The method of claim 15, wherein the pharmaceutical composition is administered by an intramuscular route.

18. The method of claim 2, wherein the pharmaceutical composition is administered to the patient for at least one week.

19. The method of claim 2, wherein the pharmaceutical composition is administered to the patient for at least 4 weeks.

20. The method of claim 2, wherein the pharmaceutical composition is administered to the patient for at least 6 weeks.

21. The method of claim 2, wherein the pharmaceutical composition is administered to the patient for at least 8 weeks.

22. The method of claim 2, wherein the pharmaceutical composition is administered to the patient at least once daily.

23. The method of claim 2, wherein the pharmaceutical composition is administered to the patient in two doses per day.

24. The method of claim 2, wherein the pharmaceutical composition is administered to the patient in three doses per day.

25. The method of claim 2, wherein the pharmaceutical composition is administered to the patient in four doses per day.

26. The method of claim 2, wherein the pharmaceutical composition is administered by a route selected from the group consisting of oral, intravenous, trans-mucosal, pulmonary, transdermal, ocular, buccal, sublingual, intraperitoneal, intrathecal, and intramuscular routes.

27. The method of claim 26, wherein the pharmaceutical composition is administered by an oral route.

28. The method of claim 26, wherein the pharmaceutical composition is administered by an intramuscular route.