First-In-Class Melatonin MT2 Receptor Agonist for Neuropathic Pain: Investigational New Drug (IND) – Enabling Studies

Challenge: Neuropathic pain is a chronic pain disorder that can develop as a result of nerve damage caused by various medical conditions. Available treatments are very limited, and patients resort to using opioids to manage their pain, leading to dependence, tolerance and the so-called opioid-induced hyperalgesia, which is characterized by an increased pain after prolonged use of opioids. Research on novel analgesic drugs for the management of neuropathic pain is, therefore, a priority.

Solution: In order to meet this need, the team designed and synthesized a novel class of drugs that selectively target the MT2 melatonin receptor (called “MT2 receptors partial agonists”) . These drugs have potent analgesic properties and provide a unique and innovative method for treating both acute and chronic neuropathic pain. While a lead candidate (UCM924) was previously identified and validated in animal models by the team, the purpose of the current project is to pursue the pharmacological characterization of their lead candidate and discover a derivate that can be orally delivered. The team will thus provide complete in vivo, in vitro, pharmacokinetics and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicology) studies to support the clinical development of this new class of drugs, as required by regulatory agencies.

Expected Achievements/Impact: MT2 melatonin receptor partial agonists represent first-in-class compounds which are effective in treating neuropathic pain and have a unique competitive advantage since it does not induce addiction nor motor effects. Upon completion of the present project, it is strongly expected that the new drug candidate will be brought to Phase I and II clinical trials. As a result, the project has already attracted the attention of private Quebec investors and Quebec pharmaceutical companies, including Delmar Chemicals Inc.