Cyclic-GluR6 analogs, methods of treatment and use
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.
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.