News & Events

When

Date - November 6, 2015
1:00 pm

What

Assistant Professor of Pharmaceutical Sciences
Concordia University Wisconsin School of Pharmacy

“Making a Better Morphine: Two Approaches to Avoiding Analgesic Tolerance”

Abstract:

The isolation of morphine as the active principle of Papaver somniferum by Sertürner in 1805 revolutionized the clinical treatment of pain. In the 200 years since this discovery, opioid analgesics remain the “gold standard” treatment of chronic severe pain in the United States. Though morphine and other mu opioid receptor (MOR) agonists are effective at alleviating pain and leaving patients in a state of well-being, tolerance to analgesic effects occurs quite rapidly, necessitating the need to administer ever-increasing doses of these powerful narcotics. For these reasons, the development of opioids lacking analgesic tolerance would represent a significant contribution to pain management. In this seminar, I will discuss two approaches that we have used as medicinal chemists to counteract analgesic tolerance development to morphine. In the first, we have altered the structure of morphine to limit its ability to interact with P-glycoprotein (P-gp), an efflux transporter that prevents morphine from entering into the brain. The resulting agents are important probes to test our hypothesis that P-gp plays a role in analgesic tolerance. In our second approach, we have designed novel compounds that act simultaneously as MOR agonists and delta opioid receptor (DOR) antagonists. Compounds containing this pharmacologic profile are understood to produce less tolerance than selective MOR agonists. We hope that this collaborative academic approach to drug discovery will facilitate the development of the next generation of analgesics.