Pharmaceutical compositions for the treatment of movement disorders

• US 20040157926A1
• Filed: 12/23/2003
• Published: 08/12/2004
• Est. Priority Date: 02/06/2003
• Status: Active Grant

• Current Assignee: Sarah Herzog Memorial Hospital Ezrat Nashim Association
• Original Assignee: Sarah Herzog Memorial Hospital Ezrat Nashim Association
• Inventors: Heresco-Levy, Uriel, Javitt, Daniel C.
• Granted Patent: US 8,629,105 B2
• Time in Patent Office: Days
• US Class Current: 514/561
• 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 31/42 Oxazoles
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/06 Anti-spasmodics
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

The invention provides a pharmaceutical composition, medical food, dietary supplement or micronutrient for the treatment of a movement disorder comprising an NMDAR agonist or partial agonist as active ingredient therein in combination with a pharmaceutically acceptable carrier.

Claims

1. A pharmaceutical composition, medical food, dietary supplement or micronutrient for the treatment of a movement disorder comprising an NMDAR agonist or partial agonist as active ingredient therein in combination with a pharmaceutically acceptable carrier.

2. A pharmaceutical composition according to claim 1 wherein said movement disorder is Parkinsons disease.

3. A pharmaceutical composition, medical food, dietary supplement or micronutrient according to claim 1 wherein the glycine-site agonists are selected from the group consisting of glycine and D-serine.

4. A pharmaceutical composition, medical food, dietary supplement or micronutrient according to claim 1 wherein the glycine-site agonists are selected from the group consisting of precursors to glycine, D-serine and D-cycloserine.

5. Use of NMDAR agonists and partial agonists for the manufacture of a pharmaceutical composition, medical food, dietary supplement or micronutrient for the treatment of movement disorders.

6. A method for the treatment of a movement disorder comprising administering to a patient a a therapeutically effective amount, for alleviating motor disorder symptoms, of an agonist or partial agonist of the glycine-site of an NMDA receptor.

7. The method of claim 6 in which NMDAR agonists and partial agonists are administered at a dose sufficient to augment NMDAR mediated neurotransmission.

8. The method of claim 6 in which NMDAR agonists target the glutamate binding site of the NMDAR complex.

9. The method of claim 6 in which NMDAR agonists target the polyamine binding site of the NMDA complex.

10. The method of claim 6 in which NMDAR agonists target the glycine binding site of the NMDAR complex.

11. The method of claim 6 in which the glycine-site agonists are selected from a group that includes glycine or d-serine.

12. The method of claim 6 in which agents are used that are precursors to glycine, d-serine or d-cycloserine.

13. The method of claim 6 in which partial agonists of the NMDA-associated glycine binding site are used in place of glycine-site full agonists.

14. The method of claim 6 in which glycine transport inhibitors are used in place of glycine agonists at doses sufficient to augment NMDAR-mediated neurotransmission.

15. The method of claim 14 in which the glycine transport inhibitors inhibit transport at GLYT1- or GLYT2-type glycine transporters.

16. The method of claim 14 in which the glycine transport inhibitors inhibit transport at System A, System L, System ASC, System N.

17. The method of claim 6 in which D amino acid oxidase inhibitors are used in place of glycine-site agonists at doses sufficient to augment NMDAR-mediated neurotransmission.

18. The method of claim 6 in which serine hydroxymethyltransferase or serine racemase modulators are used in place of glycine-site agonists at doses sufficient to augment NMDAR-mediated neurotransmission.

19. The method of claim 6 in which glycine is used at a dose of between 15 and 150 g per day.

20. The method of claim 6 in which d-serine is used at a dose of 250 mg-20 g per day.

21. The method of claim 6 in which d-cycloserine is used at a dose of 25 mg-1000 mg per day.

22. The method of claim 6 in which NMDAR agonists are added to other medications known to be effective in treatment of movement disorders, selected from the group consisting of L-dopa and other dopaminergic agents, anticholinergics, adenosine modulators, NMDA antagonists and combinations thereof.

23. The method of claim 6 in which the movement disorder is the result of treatment with antipsychotic medication.

24. The method of claim 23 in which the movement disorder is drug-induced Parkinsonism, akathasia, or tardive dyskinesia.

25. The method of claim 6 where the movement disorder is the result of neurological illness.

26. The method of claim 25 where the movement disorder is Parkinsons disease, Huntingtons chorea, Wilsons disease, Tourette'"'"'s disease, tic disorders, or obsessive-compulsive disorder.

27. A pharmaceutical composition for the treatment of a movement disorder comprising a prodrug of an NMDAR agonist or precursor thereof as active ingredient therein in combination with a pharmaceutically acceptable carrier.

28. A method for the treatment of a movement disorder comprising administering to a patient a therapeutically effective amount, for alleviating motor disorder symptoms, of a prodrug of an NMDAR agonist or precursor thereof.