Methods for increasing schwann cell survival

• US 6,417,160 B1
• Filed: 10/13/1998
• Issued: 07/09/2002
• Est. Priority Date: 10/14/1997
• Status: Expired due to Fees

• Current Assignee: Nadine A. Tatton, William G. Tatton
• Original Assignee: Nadine A. Tatton, William G. Tatton
• Inventors: Tatton, Nadine A., Tatton, William G.
• Primary Examiner(s): Davenport, Avis M.
• Application Number:
  US09/170,460
• Time in Patent Office: 1,365 Days
• Field of Search: 514/654, 514/2, 530/300, 530/303
• US Class Current: 514/6.9
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/195 having an amino group

Abstract

Methods for increasing Schwann cell survival are disclosed. The methods of the invention are useful for the treatment of conditions such as peripheral neuropathies, including diabetic neuropathies.

Claims

1. A method for increasing survival of Schwann cells in a patient as a prophylactic treatment for diabetic peripheral neuropathy, comprising administering an effective amount of a deprenyl compound to said patient wherein said survival of Schwann cells is increased as a prophylactic treatment for diabetic peripheral neuropathy.

2. The method of claim 1, wherein the deprenyl compound is represented by the structure:

in which

R₁ is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;

R₂ is hydrogen or alkyl;

R₃ is a single bond, alkylene, or —

(CH₂)_n—

X—

(CH₂)_m;

in which X is O, S, or N-methyl;

m is 1 or 2; and

n is 0,1, or 2;

R₄ is alkyl, alkenyl, alkynyl, heterocyclyl, aryl or aralkyl; and

R₅ is alkylene, alkenylene, alkynylene and alkoxylene; and

R₆ is C₃-C₆ cycloalkyl or

3. The method of claim 2, wherein R₁ is a group that can be removed in vivo.

4. The method of claim 2, wherein R₁ is hydrogen.

5. The method of claim 2, wherein R₁ is alkyl.

6. The method of claim 2, wherein R₁ is methyl.

7. The method of claim 2, wherein R₂ is methyl.

8. The method of claim 2, wherein R₃ is methylene.

9. The method of claim 2, wherein R₄ is aryl.

10. The method of claim 2, wherein R₄ is phenyl.

11. The method of claim 2, wherein R₅ is methylene.

12. The method of claim 2, wherein R₆ is

13. The method of claim 2, wherein the deprenyl compound is represented by the structure:

in which

R₁ is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;

R₂ is hydrogen or alkyl;

R₃ is a bond or methylene; and

R₄ is aryl or aralkyl;

or

R₂ and R₄—

R₃ are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group;

and pharmaceutically acceptable salts thereof.

14. The method of claim 2, wherein the deprenyl compound is represented by the structure:

in which

R₂ is hydrogen or alkyl;

R₃ is a bond or methylene; and

R₄ is aryl or aralkyl;

or

R₂ and R₄—

R₃ are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group; and

R₅ is alkylene alkenylene, alkynylene and alkoxylene;

,

and pharmaceutically acceptable salts thereof.

15. The method of claim 2, wherein the deprenyl compound is, represented by the structure:

in which

R₁ is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;

A is a substituent independently selected for each occurence from the group consisting of halogen, hydroxyl, alkyl, alkoxyl, cyano, nitro, amino, carboxyl, —

CF₃, or azido;

n is 0 or an integer from 1 to 5;

and pharmaceutically acceptable salts thereof.

16. The method of claim 1, wherein said patient is a human.

17. The method of claim 1, wherein said deprenyl compound is (−

)-desmethyldeprenyl.

18. A method for treating a patient with diabetic peripheral neuropathy, comprising administering to said patient an effective amount of a deprenyl compound, wherein said peripheral neuropathy is treated in a patient.

19. The method of claim 18, wherein said deprenyl compound is (−

)-desmethyldeprenyl.

20. The method of claim 18, wherein said neuropathy is selected from the group consisting of diabetic neuropathy and AIDS-related neuropathy.

21. The method of claim 18, wherein said patient is a human.

22. A method for increasing Schwann cell survival in a patient for use as a prophylactic treatment in diabetic peripheral neuropathy, comprising contacting a Schwann cell with a deprenyl compound, wherein said Schwann cell survival increases to indicate prophylactic treatment in diabetic peripheral neuropathy.

23. The method of claim 22, wherein said patient is a human.

24. The method of claim 22, wherein the deprenyl compound is (−

)-desmethyldeprenyl.

25. The method of claim 24, wherein the (−

)-desmethyldeprenyl is administered transdermally to the patient.

26. A method for treating diabetic peripheral neuropathy in a patient, comprising administering to said patient an effective amount of a deprenyl compound, wherein said peripheral neuropathy is treated.