SIGMA LIGANDS FOR USE IN THE PREVENTION AND/OR TREATMENT OF POST-OPERATIVE PAIN

• US 20120302568A1
• Filed: 02/04/2011
• Published: 11/29/2012
• Est. Priority Date: 02/04/2010
• Status: Active Grant

• Current Assignee: Laboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
• Original Assignee: Laboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
• Inventors: Vela Hernández, José Miguel, Zamanillo-Castanedo, Daniel, Puig Riera de Conias, Margarita
• Granted Patent: US 9,844,516 B2
• Time in Patent Office: Days
• US Class Current: 514/236.5
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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

The invention refers to the use of a sigma ligand, particularly a sigma ligand of formulae (I), (II) or (III) to prevent and/or treat acute and chronic pain developed as a consequence of surgery, especially superficial and/or deep pain secondary to surgical tissue injury, and peripheral neuropathic pain, neuralgia, allodynia, causalgia, hyperalgesia, hyperesthesia, hyperpathia, neuritis or neuropathy secondary to surgical procedure.

Claims

1. A method of treatment of a patient suffering from pain developed as a consequence of surgery, or a patient likely to suffer pain as a result of a surgical treatment, which comprises administering to the patient in a therapeutically effective amount of a sigma ligand.

2. The method according to claim 1, wherein the pain is acute and/or chronic pain developed as a consequence of surgery.

3. The method according to claim 1 wherein the sigma ligand is a sigma receptor antagonist.

4. The method according to claim 1, wherein the sigma ligand has the general formula (I):

5. The method according to claim 4, wherein R₁ is selected from H, —

COR₈ and substituted or unsubstituted alkyl.

6. The method according to claim 4, wherein R₂ is H or alkyl.

7. The method according to claim 4, wherein R₃ and R₄ together form a fused naphthyl ring system.

8. The method according to claims 4, wherein R₅ and R₆ together form a morpholine-4-yl group.

9. The method according to claim 4, wherein the sigma ligand is 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine, or a pharmaceutically acceptable salt, isomer, prodrug or solvate thereof.

10. The method according to claim 4, wherein the sigma ligand is 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine hydrochloride.

11. The method according to claim 1, wherein the sigma ligand has the general formula (II):

12. The method according to claim 11, wherein at least one of R₁ to R₃ is hydrogen or halogen.

13. The method according to claim 11, wherein R₄ is an alkyl.

14. The method according to claim 1, wherein the sigma ligand has the general formula (III):

15. The method according to claim 14, wherein R₄ is hydrogen or alkyl.

16. The method according to claim 2, wherein the pain is superficial and/or deep pain secondary to surgical tissue injury, and/or neuropathic pain, neuralgia, allodynia, causalgia, hyperalgesia, hyperesthesia, hyperpathia, neuritis or neuropathy secondary to surgical procedure.

17. The method according to claim 3, wherein the sigma ligand is selected from the group consisting of a neutral antagonist, an inverse agonist and a partial antagonist.