Federal grant · project grant (b)
In Vivo Characterization of 5-HT7 Modulators in Rat Models of Opioid Use Disorder - Opioid Analgesics (e.g. Fentanyl, Morphine, Oxycodone) Are Widely Used to Treat and Manage Moderate to Severe Acute Pain Resulting From Trauma or Surgery as Well as Some Types of Chronic Pain. It Is Well Established That These Drugs Exert Their Influence Through Activation of the Μ-opioid Receptor. Unfortunately, Opioids Are Also Highly Addictive and Physical Dependence on These Drugs Can Be Established After as Little as a Few Days of Sustained Use. Between 1999 and 2020, >565,000 People Died From an Opioid Involved Overdose, and in 2022 Nearly 70% of Drug Overdose Deaths (~74K of ~108K) Involved Synthetic Opioids, Primarily Fentanyl. in Addition, According to the National Survey on Drug Use and Health, ~2.7 Million People Were Suffering With Opioid Use Disorder (OUD) in 2020 and the Economic Impact of the Opioid Crisis in the Us Was ~$1.5 Trillion. Although Treatments Such as Methadone (dolophine), Buprenorphine (subutex) and Naltrexone (REVIA) Are Available, Only 24% of Oud Patients Received Treatment in 2022 and the Risk of Relapse Is High. the Danger of Long-term Opioid Use Extends Beyond the Risk of Overdose Death, as Patient Experiencing Oud Are at Increased Risk for a Wide Range of Additional Negative Health Consequences. There Is a Clear, Present, and Persistent Need to Develop Novel Therapies for Oud. Studies Demonstrate That Antagonism of the 5-HT7 Receptor Can Regulate Key Dopamine Pathways Involved in Substance Use Disorder and Improve Cognitive Flexibility and Memory. These Improvements Are Especially Noted in Assays With Links to Negative States Such as Psychosis, Depression, Stress, and Withdrawal. We Have Identified a Series of Novel, Drug-like 5-HT7 Antagonists That Include a Lead Compound, PRA078, Which Produces a Statistically Significant Reduction in a Cue-induced Reinstatement Rat Model of Cocaine Use Disorder. in This Program, We Will Determine the Impact of Our Lead Compound on Rat Models of Opioid Use Disorder. This Data Will Support Our Continued Advancement of This Compound Into Pre-clinical Ind Enabling Studies as a Treatment for Opioid Use Disorder.
Committed
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