Date of Award
From 2001 to 2013, worldwide prescriptions of opioids more than doubled from around 3 billion daily opioid doses per year to 7 billion due to major shifts in pain management culture and attitude.1 This surge in opioid prescriptions brought quick pain relief to patients, but it also brought new challenges, such as nonmedical opioid use, opioid use disorders, and overdose deaths.2 In 2015, 33,091 of the 52,404 drug overdose deaths were contributed to opioids, and in 2013, the cost of opioid overdose and addiction was estimated to be $78 billion in economic burden.3,4 The social and economic consequences of opioid abuse and addiction highlight the need to find alternative analgesics. There are four opioid receptors found throughout the nervous system: mu opioid receptor (MOR), kappa opioid receptor (KOR), delta opioid receptor (DOR), and nociception opioid receptor (NOR).5 Most prescribed opioids act as MOR agonists, but while they are effective analgesics, their side effects, such as addiction, have generated interest in exploring pain management ligands for the other opioid receptors.6 Salvinorin A, the main active ingredient of the hallucinogenic plant Salvia Divinorum, is one of the most potent, naturally occurring opioid agonists, and has a high affinity and selectivity toward KOR. This potent agonism toward KOR has led to unwanted side effects of salvinorin A, such as hallucination, and its effects only last 10–15 minutes due to the quick hydrolysis of the C2 ester in its structure. However, despite the side effects, salvinorin A is an important prototype for the development of drug candidates.7 Our lab has recently synthesized salvimadol, an analogue of salvinorin A with an amide linkage. Salvimadol has shown similar potency in agonistic activity toward KOR to that of salvinorin A. Our efforts are now concentrated on upscaling salvimadol production for pharmacokinetic studies as well as pain, anxiety, and depression testing. We also aim to synthesize and study several salvimadol analogues for these disorders.
McCaughan, Seth, "Synthesis of Salvimadol Analogues for the Studies of Pain, Anxiety, and Depression" (2023). Honors Theses. 3012.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 International License.
Available for download on Friday, June 26, 2026