Selective A3 Adenosine Receptor Agonists for the Treatment of Chronic Neuropathic Pain and Other Conditions

This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. A3AR agonists have been a promising strategy for the treatment of various diseases. A3AR agonists can reverse neuropathic pain by modulating the production of anti-inflammatory cytokines such as IL-10. A3AR agonists can also induce apoptosis of cancer and inflammatory cells by disrupting the Wnt and NF-KB signaling pathways. The current invention includes A3AR-selective agonists that are methanocarba derivatives. This class of compounds has been shown to be highly selective for A3AR (>3000-fold affinity versus A1AR and A2AAR). This selectively is retained in mice (400-fold affinity versus A1AR), facilitating preclinical development.