Methods for treating neuropsychiatric disorders

• US 6,420,351 B1
• Filed: 04/13/2001
• Issued: 07/16/2002
• Est. Priority Date: 04/14/1998
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: General Hospital Corporation
• Inventors: Coyle, Joseph, Tsai, Guochuan
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US09/834,351
• Publication Number:
  US 20020035145A1
• Time in Patent Office: 459 Days
• Field of Search: 514/380, 514/561, 514/114
• US Class Current: 514/114
• 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, close 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- or L-phosphoserine.

Claims

1. A pharmaceutical composition comprising (i) at least one compound selected from the group consisting of D-phosphoserine and L-phosphoserine and (ii) a second therapeutic agent selected from the group consisting of antipsychotics, antidepressants, psychostimulants, and Alzheimer'"'"'s disease therapeutics.

2. The pharmaceutical composition of claim 1, wherein the second therapeutic agent is an antipsychotic selected from the group consisting of typical antipsychotics, atypical antipsychotics, and depot antipsychotics.

3. The pharmaceutical composition of claim 1, wherein the second 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, Velafaxine XR, Dextroamphetamine, Methamphetamine, Methylphenidate, Pemoline, Donepezil, Tacrine, Acetoplenazine, Chlorprothixene, Droperidol, Pimozide, Butaperazine, Carphenazine Remoxipride, Piperacetazine, Sulpiride, and Ziprasidone.

4. A method for treating a neuropsychiatric disorder characterized by attenuated NMDA neurotransmission in a patient, the method comprising identifying a patient suffering from the neuropsychiatric disorder and administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of D-phosphoserine and L-phosphoserine.

5. The method of claim 4, wherein compound is administered at a dosage equivalent to 100 μ

g-100 g of D-serine.

6. The method of claim 4, wherein the compound is administered at a dosage equivalent to 10 mg to 100 g of D-serine.

7. The method of claim 4, where the compound is administered at a dosage equivalent to 1 mg-100 mg of D-serine.

8. The method of claim 4, wherein the compound is administered at a dosage equivalent to 10 mg-10 g of D-serine.

9. The method of claim 4, wherein the compound is administered at a dosage equivalent to 10 mg-500 mg of D-serine.

10. The method of claim 4, further comprising administering to the patient a second therapeutic agent selected from the group consisting of antipsychotics, antidepressants, psychostimulants, and Alzheimer'"'"'s disease therapeutics.

11. The method of claim 4, wherein the compound is D-phosphoserine.

12. The method of claim 4, wherein the compound is L-phosphoserine.

13. The method of claim 4, wherein the neuropsychiatric disorder is selected from the group consisting of Alzheimer'"'"'s disease, autism, depression, benign forgetfulness, a childhood learning disorder, attention deficit disorder, and close head injury.

14. The method of claim 4, wherein the compound is administered to the patient by a method selected from the group consisting of oral, intravenous, trans-mucosal, nasal, vaginal, pulmonary, transdermal, ocular, buccal, sublingual, intraperitoneal, intrathecal, intramuscular, or long term depot preparation.

15. A method of treating schizophrenia, the method comprising identifying a patient having schizophrenia and treating the patient with a therapeutically effective amount of a precursor of a compound selected from the group consisting of D-phosphoserine and L-phosphoserine.

16. The method of claim 15, wherein the compound is administered at a dosage equivalent to 100 μ

g-100 g of D-serine.

17. The method of claim 15, wherein the compound is administered at a dosage equivalent to 1 mg-100 mg of D-serine.

18. The method of claim 15, wherein the compound is administered at a dosage equivalent to 10 mg-100 g of D-serine.

19. The method of claim 15, wherein the compound is administered at a dosage equivalent to 10 mg-10 g of D-serine.

20. The method of claim 15, wherein the compound is administered at a dosage equivalent to 10 mg-500 mg of D-serine.

21. The method of claim 15, wherein the compound is D-phosphoserine.

22. The method of claim 15, wherein the compound is L-phosphoserine.

23. The method of claim 15, wherein the compound is administered to the patient by a method selected from the group consisting of oral, intravenous, trans-mucosal, nasal, vaginal, pulmonary, transdermal, ocular, buccal, sublingual, intraperitoneal, intrathecal, intramuscular, or long term depot preparation.