Alkaline and acid phosphatase inhibitors in treatment of neurological disorders

• US 5,567,724 A
• Filed: 06/01/1994
• Issued: 10/22/1996
• Est. Priority Date: 06/01/1993
• Status: Expired due to Term

• Current Assignee: RespireRx Pharmaceuticals, Inc.
• Original Assignee: RespireRx Pharmaceuticals, Inc.
• Inventors: Kelleher, Judith A., Eveleth, David D.
• Primary Examiner(s): Burn, Brian
• Application Number:
  US08/252,109
• Time in Patent Office: 874 Days
• Field of Search: 514/372, 514/263, 514/410, 514/368, 514/568
• US Class Current: 514/368
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/305 Mercury compounds
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 33/16 Fluorine compounds
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides a method of inhibiting β-amyloid toxicity in brain cells. The method includes administering to the cells an amount of an alkaline phosphatase inhibitor which is pharmacologically effective to reduce degeneration in the cells. Methods of treatment of peripheral neuropathy are also provided using acid or alkaline phosphatase inhibitors.

Claims

1. A method of inhibiting β

-amyloid toxicity in brain cells exposed to β

-amyloid peptide, comprising;

administering to said cells an arylimidothiazole derivative having nucleotide alkaline phosphatase inhibitory activity in an amount effective to reduce cell degeneration.

2. The method of claim 1, wherein said brain cells are located in a living organism suffering from a neurologic disorder.

3. The method of claim 2, wherein said neurologic disorder is Alzheimer'"'"'s Disease.

4. The method of claim 1, wherein said brain cells are located in a living organism suffering from an amyloidogenic disease associated with β

-amyloid protein.

5. The method of claim 4, wherein said amyloidogenic disease is Downs Syndrome or Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type.

6. The method of claim 1, wherein said brain cells are located in vitro.

7. The method of claim 2, wherein the administering step comprises administering said arylimidothiazole derivative orally, intravenously, intraperitoneally, intramuscularly, by injection into cerebrospinal fluid, by injection into an intracerebral ventricle, or via a carrier protein.

8. The method of claim 2, wherein said arylimidothiazole derivative is administered at a dose of from approximately 0.01 mg/kg to 5 mg/kg body weight per day.

9. The method of claim 1, wherein said arylimidothiazole derivative is selected from the group consisting of levamisole, bromolevamisole and bromotetramisole.

10. A method of treating a human subject having a peripheral neuropathy, comprising:

administering to said subject an amount of a nucleotide alkaline phosphatase inhibitor which is pharmacologically effective to alleviate the symptoms of the peripheral neuropathy.

11. The method of claim 10, wherein the administering step comprises administering said alkaline phosphatase inhibitor orally, intravenously, intraperitoneally, or intramuscularly.

12. The method of claim 10, wherein said alkaline phosphatase inhibitor is administered at a dose of from approximately 0.001 mg/kg to 10 mg/kg body weight per day.

13. The method of claim 10, wherein said alkaline phosphatase inhibitor is an arylimidothiazole derivative.

14. The method of claim 13, wherein said arylimidothiazole derivative is selected from the group consisting of levamisole, bromolevamisole and bromotetramisole.

15. A method of treating a human subject having a peripheral neuropathy, comprising:

administering to said subject an amount of an acid phosphatase inhibitor which is pharmacologically effective to alleviate the symptoms of the peripheral neuropathy.

16. The method of claim 15, wherein the administering step comprises administering said acid phosphatase inhibitor orally, intravenously, intraperitoneally, or intramuscularly.

17. The method of claim 15, wherein said acid phosphatase inhibitor is administered at a dose of from approximately 0.001 mg/kg to 10 mg/kg body weight per day.

18. The method of claim 15, wherein said acid phosphatase inhibitor is para-chloromercuribenzoate (pCMB) or an inorganic salt of tartrate or fluoride.

19. The method of claim 18, wherein said inorganic salt is selected from the group consisting of Na;

K; and

Na,K.