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Claims for Patent: 5,614,560

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Claims for Patent: 5,614,560

Title: Method of preventing NMDA receptor-mediated neuronal damage
Abstract:Disclosed is a method for reducing non-ischemic NMDA receptor-mediated neuronal damage in a mammal by administering to the mammal a compound of the formula shown in FIG. 1 (or a physiologically-acceptable salt thereof), wherein R.sub.1 includes an amino group, R.sub.2 -R.sub.17 are independently H or a short chain aliphatic group comprising 1-5 carbons, and R.sub.4 and R.sub.10 also may (independently) be a halogen or an acyl group. Also disclosed is a screen for antagonists of NMDA receptor mediated neurotoxicity which have an enhanced prospect for being clinically tolerated and selective against such neurotoxicity.
Inventor(s): Lipton; Stuart A. (Newton, MA)
Assignee: Children's Medical Center Corporation (Boston, MA)
Application Number:08/419,672
Patent Claims: 1. A method for reducing non-ischemic NMDA receptor-mediated neuronal degeneration in a mammal, comprising administering to said mammal a compound of the formula shown below: ##STR2## wherein R.sub.1 comprises an amino group; R.sub.2 -R.sub.17 are independently H or a short chain aliphatic group comprising 1-5 carbons; and R.sub.4 and R.sub.10 may also (independently) be a halogen or an acyl group, or a physiologically acceptable salt thereof, in a concentration effective to cause such reduction.

2. The method of claim 1, wherein R.sub.1 is NH.sub.2.

3. The method of claim 2, wherein said compound is amantadine.

4. The method of claims 1 or 2, wherein R.sub.4 is a methyl group.

5. The method of claims 1 or 2, wherein R.sub.10 is a methyl group.

6. The method of claim 1, wherein said R.sub.4 and R.sub.10 are methyl groups.

7. The method of claim 6, wherein said R.sub.1 is NH.sub.2.

8. The method of claim 7, wherein said compound is memantine.

9. The method of claim 1, wherein R.sub.1 is ##STR3## wherein X.sub.1 and X.sub.2 are independently H or a short chain aliphatic group comprising between 1-5 carbons.

10. The method of claim 9, wherein X.sub.1 and X.sub.2 are H and CH.sub.3, respectively, or wherein X.sub.1 and X.sub.2 are CH.sub.3 and H, respectively.

11. The method of claim 10, wherein said compound is rimantadine.

12. The method of claim 9, wherein R.sub.4 is a methyl group.

13. The method of claim 9, wherein R.sub.10 is a methyl group.

14. The method of claim 9, wherein R.sub.4 and R.sub.10 are methyl groups.

15. The method of claim 1 wherein said mammal has Huntington's disease or amyotrophic lateral sclerosis.

16. The method of claim 1 wherein said mammal has a condition selected from the group consisting of: neurolathyrism; Guam disease; olivo-pontocerebellar atrophy; hyperglycinemia; hepatic encephalopathy; uremic encephalopathy; 4-hydroxybuturic aciduria; MELAS syndrome; Rett syndrome; homocysteinuria; hyperprolinemia; and peripheral neuropathy.

17. The method of claim 1 in which said mammal is subject to a long-term non-ischemic neurodegenerative disease.

18. The method of claim 1 in which said mammal is subject to central nervous system trauma.

19. The method of claim 1 in which said mammal is subject to poisoning from carbon monoxide, lead, or domoic acid.
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