Thomas Prince
Pronouns:
Research Mentor(s): John Traynor
Research Mentor School/College/Department: /
Program: RS
Session: Session 2 (10:00am – 10:50am)
Authors: Thomas Prince, Kelsey Kochan, John Traynor
Abstract
Opioid analgesics, such as fentanyl, have many clinical uses in treating pain. They act by binding to mu-opioid receptors (MOR), resulting in pain relief. However, this interaction with MOR comes with many on-target adverse effects, namely constipation, addiction liability, and the fatal effect in the event of an overdose, respiratory depression. Thus, there is an unmet need for safer analgesics in pain management. One potential alternative approach to traditional pain therapeutics is positive allosteric modulation. This method would utilize compounds that bind to an alternate site at MOR than the typical orthosteric site where clinically used opioid drugs interact. These allosteric modulators can change how ligands interact with MOR by altering their binding affinity, potency, and efficacy. Positive allosteric modulators (PAMs) enhance these characteristics. If used in combination with traditional opioids, PAMs could allow for opioid sparing in clinical settings. In this project, we examine the ability of one particular PAM, BMS-122, to enhance both the beneficial and adverse effects of clinically used opioids, such as fentanyl. BMS-122 has been shown to enhance the antinociceptive, or pain relieving, effects of fentanyl in the mouse warm water tail withdrawal assay without enhancing opioid- induced constipation. We plan to examine whether BMS-122 alters other opioid-induced adverse effects, namely respiratory depression and addiction liability. We hypothesize that BMS-122 will not impact the development or severity of adverse effects induced by fentanyl. Overall, if BMS-122 can enhance MOR-mediated antinociception without potentiating additional adverse effects, it would further encourage the potential clinical utility of MOR PAMs.
