Design and Development of Salvinorin-Based Ligands for Opioid Receptors
Ph.D. in Pharmaceutical Sciences
The proposed research will entail using an isolate of known natural product from Salvia divinorum, salvinorin A, as a probe to determine what structural modifications will lead to a change in the affinity and selectivity towards each individual opioid receptor as well as the investigation of which interactions are critical for the selectivity. After the semi-synthesis of our proposed compounds is done, in vitro studies will be completed to determine their affinity and functional activity (agonism or antagonism)to the four opioid receptors. We will then complete computer modeling of our compounds on these receptors to determine what receptor-scaffold interactions are crucial to binding at their respective opioid receptors. Concurrently, we will be completing in vivo assays for pain, depression, anxiety, and/or drug withdrawal dependent upon the activity determined in vitro of the several compounds that I have already made. We believe that by successfully completing this study, we will be able to obtain a more complete picture of how this interesting scaffold works and potentially optimize lead compounds for the various disease states associated with the four opioid receptors.
Akins, Nicholas, "Design and Development of Salvinorin-Based Ligands for Opioid Receptors" (2019). Graduate Student Council Research Grants. 30.