Methods for treating neuropsychiatric disorders

• US 7,704,978 B2
• Filed: 07/05/2005
• Issued: 04/27/2010
• 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:
  US11/175,832
• Publication Number:
  US 20050250851A1
• Time in Patent Office: 1,757 Days
• Field of Search: 514/119, 514/380, 514/561
• US Class Current: 514/119
• 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 a neuropsychiatric disorder in a patient, the method comprising administering to a patient suffering from a neuropsychiatric disorder a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of N-methylglycine, a salt of N-methylglycine, an ester of N-methylglycine, alkylated N-methylglycine, and a precursor of N-methylglycine, wherein the pharmaceutical composition is administered at a dose equivalent to 10 mg to 10 g N-methylglycine per day.

2. The method of claim 1, wherein the neuropsychiatric disorder is schizophrenia.

3. The method of claim 1, wherein the compound is N-methylglycine.

4. The method of claim 1, wherein the compound is a salt of N-methylglycine 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 N-methylglycine.

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

6. The method of claim 1, wherein the compound is a precursor of N-methylglycine, and the precursor is N,N,N-trimethylglycine or N,N-dimethylglycine.

7. The method of claim 1, further comprising administering to the patient at least one therapeutic agent selected from the group consisting of antipsychotics, antidepressants, psychostimulants, and Alzheimer'"'"'s disease therapeutics.

8. The method of claim 7, wherein said therapeutic agent is selected from the group consisting of Chlorpromazine, Thioridazine, Mesoridazine, Fluphenazine, Perphenazine, Trifluoperazine, Thiothixene, Haloperidol, Loxapine, Molindone, Clozapine, Risperidone, Olanzapine, Quetiapine, Haloperidol decanoate, Fluphenazine decanoate, Fluphenazine enanthate, Amitriptyline, Amoxapine, Bupropion, Bupropion SR, Clomipramine, Desipramine, Doxepin, Fluoxetine, Fluvoxamine, Imipramine, Maprotiline, Mirtazapine, Nefazodone, Nortriptyline, Paroxetine, Phenelzine, Protriptyline, Sertraline, Tranylcypromine, Trazodone, Trimipramine, Venlafaxine, Venlafaxine XR, Dextroamphetamine, Methamphetamine, Methylphenidate, Pemoline, Donepezil, Tacrine, Acetophenazine, Chlorprothixene, Droperidol, Pimozide, Butaperazine, Carphenazine, Remoxipride, Piperacetazine, Sulpiride, and Ziprasidone.

9. The method of claim 8, wherein said therapeutic agent is Chlorpromazine or Risperidone.

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

11. The method of claim 1, wherein the pharmaceutical composition is administered at a dose equivalent to 100 mg to 10 g N-methylglycine per day.

12. A method for treating a positive symptom of schizophrenia, the method comprising administering to a patient suffering from a positive symptom of schizophrenia a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of N-methylglycine, a salt of N-methylglycine, an ester of N-methylglycine, alkylated N-methylglycine, and a precursor of N-methylglycine.

13. The method of claim 12, wherein the compound is N-methylglycine.

14. The method of claim 12, wherein the compound is a salt of N-methylglycine 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 N-methylglycine.

15. The method of claim 12, wherein the compound is an alkylated N-methylglycine having an alkyl group with 1-20 carbon atoms.

16. The method of claim 12, wherein the compound is a precursor of N-methylglycine, and the precursor is N,N,N-trimethylglycine or N,N-dimethylglycine.

17. The method of claim 12, further comprising administering to the patient at least one therapeutic agent selected from the group consisting of antipsychotics, antidepressants, psychostimulants, and Alzheimer'"'"'s disease therapeutics.

18. The method of claim 17, further comprising administering to the patient at least one therapeutic agent selected from the group consisting of Chlorpromazine, Thioridazine, Mesoridazine, Fluphenazine, Perphenazine, Trifluoperazine, Thiothixene, Haloperidol, Loxapine, Molindone, Clozapine, Risperidone, Olanzapine, Quetiapine, Haloperidol decanoate, Fluphenazine decanoate, Fluphenazine enanthate, Amitriptyline, Amoxapine, Bupropion, Bupropion SR, Clomipramine, Desipramine, Doxepin, Fluoxetine, Fluvoxamine, Imipramine, Maprotiline, Mirtazapine, Nefazodone, Nortriptyline, Paroxetine, Phenelzine, Protriptyline, Sertraline, Tranylcypromine, Trazodone, Trimipramine, Venlafaxine, Venlafaxine XR, Dextroamphetamine, Methamphetamine, Methylphenidate, Pemoline, Donepezil, Tacrine, Acetophenazine, Chlorprothixene, Droperidol, Pimozide, Butaperazine, Carphenazine, Remoxipride, Piperacetazine, Sulpiride, and Ziprasidone.

19. The method of claim 18, wherein the therapeutic agent is Chlorpromazine or Risperidone.

20. The method of claim 12, wherein the pharmaceutical composition is administered for at least six weeks.

21. A method for treating schizophrenia, the method comprising administering to a patient suffering from schizophrenia a pharmaceutical composition comprising a therapeutically effective amount of N,N,N-trimethylglycine or N,N-dimethylglycine.