Meriel Crowley-Wang
Pronouns: she/her
Research Mentor(s): Jessica Anand
Research Mentor School/College/Department: Pharmacology / Medicine
Program: UROPF
Session: Session 3 (11:00am – 11:50am)
Authors: Meriel Crowley-Wang , Jessica Anand
Abstract
Unintentional drug overdose, primarily from synthetic opioids, is one of the leading causes of death for Americans aged eighteen to forty-five. According to the CDC, in 2021, 71,238 deaths, of which 90% were fentanyl-related, were attributed to synthetic opioids. Current standard of care for opioid overdose, Narcan, which contains active pharmaceutical ingredient naloxone, is less effective at reversing fentanyl-related deaths, due to fentanyl’s potency and longer half-life. Opioids like fentanyl bind to the human mu opioid receptor (hMOR), inducing respiratory depression, which may result in death. Twelve DRC compounds suspected to reverse opioid overdose by blocking hMOR were identified and synthesized. A study was undertaken to establish the side effect profile for these twelve DRC compounds, in order to identify a drug candidate for an improved opioid overdose reversal treatment. Binding affinity at the human kappa opioid receptor (hKOR) was examined using a competition binding assay with radioactive 3[H] diprenorphine. At this early stage, results have not yet been obtained. It is expected that DRCs with low affinity for hKOR will induce the less negative side effects, as interactions with hKOR have been observed to produce feelings of dysphoria and psychosis-like effects. The examination of binding affinity at hKOR will help identify a drug candidate for a novel fentanyl-specific opioid rescue agent by providing a potential side effect profile.
