Alyssa Calloway
Pronouns: she/her
Research Mentor(s): John Traynor
Research Mentor School/College/Department: Pharmacology / Medicine
Program:
Authors: Alyssa Calloway, Benjamin Clements, John Traynor
Session: Session 3: 11:00 am – 11: 50 am
Poster: 55
Abstract
Opioids are commonly used to treat chronic pain, but they cause many unwanted side-effects, such as addiction and disruption of breathing, leading to death. Positive allosteric modulators (PAMs) have the ability to enhance the pain-relieving properties of opioids without enhancing the negative side effects, which in turn decreases the dose of opioid administered to treat pain. Our goal is to perform preliminary research on PAMs at certain opioid receptors to understand their mechanisms of increasing drug effect. Through the use of a cell-based luminescence assay, we are able to determine the extent to which modulators increase the effect of opioids at certain receptors by measuring light emission. Greater amount of light emitted correlates to increased inhibition of adenylyl cyclase, and therefore increased activation of the opioid receptor. The increased activation of the opioid receptor suppresses neuron activity, which is critical when treating pain. Through this research, we aim to advance the knowledge of PAMs to be able to develop more effective modulators in the future to effectively treat chronic pain. I am exploring two modulators: BMS-122 and BMS-187. It is hypothesized that both of these PAMs bind at a shared site on the mu- and delta-opioid receptors. We found that at the delta-opioid receptor BMS-122 acts as a noncompetitive antagonist for BMS-187, indicating that they act at different sites on the receptor. Additionally, our evidence suggests that at the mu-opioid receptor the action of BMS-187 is not blocked by the action of BMS-124, which means that they also act at different sites on the receptor, but do not act as noncompetitive antagonists at mu. Future trials with the kappa-opioid receptor may be run to obtain evidence pertaining to the interactions of BMS-187 and BMS-122 at this subtype. The future of this research aims to develop better pain therapies using PAMs.
