Cyclic-GluR6 analogs, methods of treatment and use

Patent metadata

Field	Value
Publication number	US-9403876-B2
Application number	US-201013320848-A
Country	US
Kind code	B2
Filing date	May 18, 2010
Priority date	May 18, 2009
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

A composition which is reversible inhibitor of at least one neuron-specific PDZ domain comprising

wherein
R is a molecular transporter with or without a linker amino acid;
R 1 is at least about one amino acid covalently bound; and,
R 2 is isoleucine, leucine, alanine, phenylalanine, or valine, and methods of use.

First claim

The invention claimed is:

1. A composition which is reversible inhibitor of at least one neuron-specific PDZ domain comprising:

where n is about 6 to 20 units.

2. A method of treatment of neuro-stress comprising administering to a subject a therapeutically effective amount of the composition of claim 1 .

3. The method of claim 2 wherein the neuro-stress is stroke.

4. The method of claim 2 wherein said administration is in advance of said neuro-stress.

5. The method of claim 2 further compromising cotreatment with a therapeutically effective amount of an NMDA receptor agonist.

6. The method of claim 5 wherein said NMDA receptor agonist is selected from the group comprising AMPA, kainate, ketamine and NMDA.

7. The method of claim 2 wherein said therapeutic effective dose of the composition of claim 1 is from about 0.1 μM to about 100 μM.

8. The method of claim 7 wherein said dosage is from about 20 μM to about 40 μM.

9. The method of claim 2 wherein administration is parenteral, oral, buccal, sublingual, or by nasal spray.

10. The method of claim 9 wherein administration is intrathecal.

11. The method of claim 6 wherein said receptor agonist is ketamine from about 10 to about 250 mg.

12. A composition which is reversible inhibitor of at least one neuron-specific PDZ domain comprising:

wherein
R is a molecular transporter including 7 contiguous arginines with or without a linker amino acid;
R 1 is at least about one amino acid covalently bound; and,
R 2 is isoleucine, leucine, alanine, phenylalanine, or valine
and having a P —4 position, and,
R 3 is one side chain moiety selected from the group consisting of lysine, arginine, glutamic acid or aspartic acid.

13. A method of treatment of neuro-stress comprising administering to a subject a therapeutically effective amount of the composition of claim 12 .

14. The method of claim 13 wherein the neuro-stress is selected from the group comprising stroke, traumatic brain injury, epilepsy, pain or neurodegenerative disease.

15. The method of claim 13 wherein said administration is in advance of said neuro-stress.

16. The method of claim 13 further compromising cotreatment with a therapeutically effective amount of an NMDA receptor agonist.

17. The method of claim 16 wherein said NMDA receptor agonist is selected from the group comprising AMPA, kainate, ketamine and NMDA.

18. The method of claim 13 wherein said therapeutic effective dose of the composition of claim 12 is from about 0.1 μM to about 100 μM.

19. The method of claim 18 wherein said dosage is from about 20 μM to about 40 μM.

20. The method of claim 13 wherein administration is parenteral, oral, buccal, sublingual, or by nasal spray.

21. The method of claim 20 wherein administration is intrathecal.

22. The method of claim 17 wherein said receptor agonist is ketamine from about 10 to about 250 mg.

Assignees

• Spaller Mark
• Marshall John
• Goebel Dennis J
• Univ Brown

Inventors

• Spaller Mark
• Marshall John
• Goebel Dennis J

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K31/135

  having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} · CPC title

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title