Lana Cerbin Eckhoff
Research Mentor: Jessica Anand
Mentor Department: Pharmacology, Medicine
Author(s): Lana Cerbin, Jessica Anand
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 93
Abstract
Opioid drugs such as morphine, hydrocodone, and fentanyl are widely used to treat pain but carry the risk of misuse, addiction, and even overdose. Opioid-related deaths continue to rise in the United States, with 105,000 opioid-involved overdose deaths occurring in 2023. There is therefore a significant unmet need for new treatments that are safer and have less abuse potential. To address this issue, assessment of opioid drug activity at the mu receptor level (MOR) is necessary, as it is responsible for both the analgesic and adverse effects of opioid drugs. This research project aims to compare binding affinities of different opioids at MOR to better understand how changes in molecular structure can impact receptor affinity. The hypothesis for this project is that one of the opioids tested will produce a lower Ki value and therefore higher MOR affinity as a result of some molecular change made to the drug structure. Higher MOR affinity indicates tighter receptor binding which may contribute to a greater overdose risk. In this study, four opioid drugs were examined using in vitro pharmacological assays to compare their interactions with MOR. The binding affinity of each drug was evaluated by measuring the Ki values at MOR membranes, which gave insight into how effectively each drug binds to the receptor. The results revealed differences in MOR binding affinity among the four opioid drugs, as well as some consistency across repeated experiments. In particular, DRC 146 produced a low Ki value, indicating high receptor affinity, whereas DRC 136 had a high Ki value and low receptor affinity. To produce safer and less addictive opioids, understanding opioid-receptor affinity is important and necessary, as demonstrated by this study. Through comparing opioid drugs using laboratory assays, this research supports the development of safer analgesics.
