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Details for Patent: 5,506,231

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Details for Patent: 5,506,231

Title: Treatment of aids dementia, myelopathy and blindness
Abstract:Damage to CNS neurons of a human patient infected with a human immunodeficiency virus is reduced by administering an antagonist of the NMDA receptor complex.
Inventor(s): Lipton; Stuart A. (Newton, MA)
Assignee: The Children's Medical Center Corporation (Boston, MA)
Filing Date:Jan 21, 1993
Application Number:08/006,326
Claims:1. A method of reducing damage to a human patient's CNS neurons incident to infection of said patient with a human immunodeficiency virus (HIV), said method comprising administering to said patient a therapeutic composition comprising a compound which is an antagonist of the NMDA receptor-channel complex and which reduces the gp120-responsive rise in free Ca.sup.++ ion concentration in said CNS neurons of said patient, in a concentration effective to cause such reduction.

2. The method of claim 1 wherein said compound is a competitive NMDA antagonist, acting at the agonist binding site.

3. The method of claim 1 wherein said compound is a un-competitive NMDA antagonist, blocking the NMDA channel.

4. The method of claim 1 wherein said compound is an NMDA antagonist operating at the glycine site of the NMDA receptor.

5. The method of claim 1 wherein said compound is an NMDA antagonist operating at the polyamine site of the NMDA receptor.

6. The method of claim 1 wherein said compound is an NMDA antagonist operating at the redox site of the NMDA receptor.

7. The method of claim 1 wherein said compound is a non-competitive NMDA antagonist.

8. The method of claim 1 wherein said compound inhibits protein kinase C activation by NMDA stimulation.

9. The method of claim 1 wherein said patient manifests symptoms of AIDS related complex or AIDS.

10. The method of claim 1 wherein said compound is administered orally or intravenously.

11. A method of reducing damage to a human patient's CNS neurons incident to infection of said patient with a human immunodeficiency virus (HIV), wherein the blood of said patient contains antibodies to HIV, said method comprising administering to said patient a therapeutic composition comprising a compound which is an antagonist of the NMDA receptor-channel complex and which will reduce the gp-120-responsive rise in free Ca.sup.++ ion concentration in said CNS neurons of said patient, said administration being effective to cause such reduction.

12. A method of reducing damage to a human patient's CNS neurons incident to infection of said patient with a human immunodeficiency virus (HIV), said method comprising administering to said patient a therapeutic amount of an NMDA receptor complex antagonist selected from the group consisting of:

a) MK-801 (dizocipline);

b) dibenzocycloheptene;

c) dextrorphan;

d) dextromethorphan; and

e) ketamine,

said administration being effective to reduce said CNS damage incident to HIV infection of said patient.

13. The method of claim 12, wherein the compound is MK-801.

14. A method of reducing damage to a human patient's CNS neurons incident to infection of said patient with a human immunodeficiency virus (HIV), said method comprising administering to said patient an uncompetitive antagonist of the NMDA receptor channel complex, said administration being effective to reduce said CNS damage incident to HIV infection of said patient.

15. A method of treatment to reduce HIV-related vision loss, myelopathy or dementia in a human subject having an HIV infection, said method comprising administering an antagonist of the NMDA receptor-channel complex to said subject so as to reduce HIV-related vision loss, myelopathy or dementia.

16. A method of treatment to reduce HIV-related central nervous system damage in a human subject having an HIV infection, said method comprising administering an antagonist of the NMDA receptor-channel complex to said subject having an HIV infection, so as to reduce HIV-related central nervous system damage.

17. The method of claim 15 or claim 16 in which the antagonist is an NMDA receptor-channel complex antagonist that is not competitive.
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