Treatment and prevention of neuropathic pain with P2Y14 antagonists
Inventors
Salvemini, Daniela • Jacobson, Kenneth Alan
Assignees
St Louis University • US Department of Health and Human Services
Publication Number
US-11708346-B2
Publication Date
2023-07-25
Expiration Date
2040-07-23
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed herein are methods for treating neuropathic pain in a subject in need thereof. The methods include: administering to a subject in need thereof a therapeutically effective amount of an antagonist of P2Y14.
Core Innovation
The invention relates to methods for treating neuropathic pain by administering antagonists of the P2Y14 receptor. The P2Y14 receptor is a G protein-coupled receptor activated by extracellular UDP-glucose and related nucleotides, which function as damage-associated molecular patterns (DAMPs). The disclosed methods include administering therapeutically effective amounts of P2Y14 antagonists, particularly compounds with a naphthalene or phenyl-triazolyl scaffold, to subjects experiencing neuropathic pain.
The background identifies neuropathic pain as a complex and difficult-to-treat condition arising from nervous system injuries caused by trauma, disease, or neurotoxins. Current treatments, such as opioids, have limitations including tolerance development, severe side effects, and abuse potential, creating an unmet need for novel non-narcotic analgesics. The methods described provide a novel approach to prevent and treat neuropathic pain by antagonizing the P2Y14 receptor, addressing the need for effective treatments with potentially improved safety profiles.
Claims Coverage
The patent includes two claims focusing on methods for treating neuropathic pain using P2Y14 antagonists with specific chemical structures.
Method of treating neuropathic pain by administering a P2Y14 antagonist of formula (III)
The method comprises administering to a subject in need a therapeutically effective amount of a P2Y14 receptor antagonist having the chemical structure defined as formula (III), which includes a conjugate with specified substituents and linkers.
Use of a carboxyethylpolyamido (CEPAM) dendron functionalized antagonist for neuropathic pain treatment
The method wherein the dendron in the formula (III) antagonist is a carboxyethylpolyamido (CEPAM) dendron optionally functionalized at least at one position with a specific moiety, enhancing the therapeutic application.
The independent claims cover administering therapeutically effective amounts of specific P2Y14 antagonist compounds, particularly those with dendron conjugates, for treating neuropathic pain, establishing the chemical scope of the invention's therapeutic methods.
Stated Advantages
P2Y14 receptor antagonists rapidly reverse mechano-allodynia in a dose-dependent manner in a mouse model of chronic neuropathic pain.
The antagonists maintain high efficacy with reduced off-target activity, providing a potentially safer alternative to opioids.
Some antagonists display prolonged in vivo efficacy, lasting several hours after administration.
The compounds act peripherally, potentially avoiding central nervous system side effects associated with blood-brain barrier penetration.
Documented Applications
Treatment of neuropathic pain resulting from peripheral nerve injury, as demonstrated in a mouse chronic constriction injury model.
Use of P2Y14 receptor antagonists for prevention and treatment of pathological pain conditions characterized by mechano-allodynia and dysesthesia.
Interested in licensing this patent?