Ava McGlashen
Pronouns: she/her
Research Mentor(s): Jessica Anand
Research Mentor School/College/Department: Pharmacology / Medicine
Program:
Authors: Ava McGlashen, Jessica Anand
Session: Session 3: 11:00 am – 11: 50 am
Poster: 21
Abstract
Opioids are commonly used to treat pain but can also lead to addiction and fatalities. Today the United States is amid an opioid epidemic and at the heart of this issue are synthetic opioids. In 2022, 68% of the 107,081 opioid deaths were caused by synthetic opioids, such as fentanyl (Centers for Disease Control). The current treatment for opioid overdose, naloxone, has a shorter half-life than fentanyl and thus, is not effective in reversing overdose. There are three receptors where opioids bind; these are named Mu, Delta, and Kappa. The tighter a compound binds to a receptor, the higher affinity it has for that receptor. Further, if a compound activates a receptor, it is considered an agonist. If it doesn’t activate a receptor, it is considered an antagonist. The activation of these receptors initiates the effects of opioids. For example, fentanyl primarily binds to the Mu receptor as an agonist, which induces effects such as respiratory depression. We started with fentanyl and made structural changes to make it an antagonist (reverse opioid overdose) instead of an agonist. To be an effective treatment for fentanyl overdose we want a compound that keeps the high affinity at Mu and the long duration of action that fentanyl has. However, we also want a compound that does not activate Delta or Kappa receptors as this could lead to adverse effects. Using competition binding, I will test the affinity at each receptor for these compounds. Comparing their affinities will signify which structural changes should be made to fentanyl. Overall, this project is a steppingstone in discovering a more effective treatment for fentanyl overdose. This will not only save lives, but also lessen the economic burden felt by the opioid epidemic.
