Muscarinic M1 receptor agonists for pain management

• US 20050130961A1
• Filed: 03/26/2004
• Published: 06/16/2005
• Est. Priority Date: 03/28/2003
• Status: Abandoned Application

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Rodriguez, Mario, Vanover, Kimberly, Davis, Robert E.
• Application Number:
  US10/809,975
• Publication Number:
  US 20050130961A1
• Time in Patent Office: Days
• US Class Current: 514/230.500
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Disclosed herein are compounds and methods for treating chronic neuropathic pain. It has been discovered that compounds that selectively interact with a muscarinic receptor subtype are effective in treating neuropathic pain. Specifically, compounds that selectively interact with the M1 muscarinic receptor subtype may be used.

Claims

1. A method for treating neuropathic pain comprising:

identifying a subject in need of such treatment; and

providing the subject with an effective amount of at least one compound that selectively activates the M(1) receptor subtype, whereby one or more symptoms of the neuropathic pain are reduced.

2. The method of claim 1, wherein the subject presents hyperalgesia.

3. The method of claim 1, wherein the subject presents allodynia.

4. The method of claim 1, wherein the neuropathic pain is associated with diabetes, viral infection, irritable bowel syndrome, amputation, cancer, or chemical injury.

5. The method of claim 1, wherein the at least one compound that selectively activates the M(1) receptor subtype does not alleviate acute pain.

6. The method of claim 1, wherein the compound is selected from the group consisting of the compounds of Formulas VII, VIII, and IX:

7. A method of identifying a compound that alleviates hyperalgesia or allodynia in a subject, comprising:

providing the subject with at least one muscarinic receptor test compound; and

determining if the at least one test compound reduces hyperalgesia or allodynia in the subject.

8. The method of claim 7, wherein the at least one test compound is selective for the M(1) or M(4) but not M(2) or M(3) receptor.

9. The method of claim 7, wherein the at least one test compound is selective for the M(1) receptor.

10. The method of claim 7, wherein the hyperalgesia is thermal hyperalgesia.

11. The method of claim 7, wherein the allodynia is tactile allodynia.

12. A pharmaceutical composition comprising an effective amount of at least one compound that selectively activates the M(1) receptor subtype in an amount effective to reduce one or more symptoms of neuropathic pain.

13. The composition of claim 12, wherein the compound is selected from the group consisting of the compounds of Formulas VII, VIII, and IX: