Thomas Prince
Pronouns: he/him
Research Mentor(s): John Traynor
Co-Presenter:
Research Mentor School/College/Department: Pharmacology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 5 – 3:40pm – 4:30 pm
Room: League Ballroom
Authors: Thomas Prince, Kelsey Kochan, John Traynor
Presenter: 43
Abstract
Opioid analgesics, such as morphine, have a wide range of clinical uses in the treatment of pain. They act by binding to mu-opioid receptors (MOR), resulting in pain relief. However, this interaction with MOR comes with a plethora of on-target adverse effects, namely constipation, addiction liability, and the fatal adverse effect, respiratory depression. Thus, there is an unmet need for safer analgesics in the treatment of chronic pain. One alternative approach to traditional pain therapeutics is positive allosteric modulation. This method would utilize a compound that binds to a site separate at MOR from the typical orthosteric site where clinically used MOR agonists interact. These allosteric modulators can change how ligands interact with MOR by altering their binding affinity, potency, and efficacy. The hypothesized result is effective pain relief with minimized risk for adverse effects. One such positive allosteric modulator, BMS-122, on its own has been shown to produce pain relief with minimal adverse effects when compared to morphine. Additionally, BMS-122 has been shown to enhance the antinociceptive effect produced by morphine in the mouse warm water tail withdrawal. With this project, we hope to discover whether BMS-122 results in altered opioid-induced adverse effects, such as constipation and respiratory depression. We hypothesize that there will be no significant difference in adverse effects between mice with BMS-122 and morphine compared with mice that are administered morphine alone. If BMS-122 can enhance MOR-mediated antinociception, but not the adverse effects, it would further encourage the potential clinical utility of MOR positive allosteric modulators.
Biomedical Sciences, Interdisciplinary
