Honors Theses

Date of Award


Document Type

Undergraduate Thesis


Biomolecular Sciences

First Advisor

Hoang V. Le

Relational Format



The number of opioid prescriptions as a method in pain management increased dramatically in the mid 1990’s following Dr. James Campbell’s 1995 Presidential address to the American Pain Society, where he called for patient pain to be included as a vital sign. The rapid increase in prescriptions in the early 2000’s coupled with a massive effort by pharmaceutical companies to downplay the addictiveness of these drugs has led to a consistent increase in opioid-related drug overdoses, with 47,600 of 70,237 drug related deaths involving opioids in 2017. Opioid analgesics most commonly act upon the mu-opioid receptor (MOR), which is one of four G-protein coupled receptors that constitute the opioid system. The remaining three are the kappa-opioid receptor (KOR), the delta-opioid receptor (DOR), and the nociceptin-opioid receptor (NOR). Theses receptors are widespread throughout both the peripheral nervous system (PNS) and the central nervous system (CNS) and are imperative in the modulation of antinociception and behavioral states such as addiction, anxiety, and depression. Salvinorin A, the primary active ingredient of the plant Salvia divinorum, is one of the most potent naturally-occurring opioid receptor KOR agonists. It has the potential to be beneficial in pain management, as well as a number of CNS disorders, but the intense hallucinogenic effects of Salvinorin A have prevented it from ever passing clinical trials. Salvinorin A has, however, served as a prototype for related drug candidates. Our lab recently discovered several Salvinorin-based ester compounds that have dual or mixed activity on opioid receptors, which have the potential for the treatment of pain, anxiety, and depression without the addictive side effects of pure MOR agonists or hallucinogenic and dissociative side effects of pure KOR agonist. In attempts to create biologically and chemically stable analogs, our lab successfully synthesized five target amide-linked salvinorin compounds that would probe how the inclusion or exclusion of heteroatoms in the 6,5-fused ring structure will confer selectivity to various opioid receptors. The preliminary binding results of these compounds confirm that the linker also plays an important role in the structure-activity relationship of the C2 binding pocket.

Available for download on Friday, September 02, 2022

Included in

Chemistry Commons