The Therapeutic Potential of Functionally Selective 5-HT₇ Receptor Ligands

Seth Y Ablordeppey

Florida A&M University College of Pharmacy and Pharmaceutical Sciences

Current statistics indicates that pain treatment with opioids continue to be a huge societal problem. For example, provisional data from CDC’s National Center for Health Statistics indicate that there were an estimated 100,306 drug overdose deaths in the United States during the 12-month period ending in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before. More than 932,000 people have died since 1999 from a drug overdose. Nearly 75% of drug overdose deaths in 2020 involved an opioid. Opioids are substances that work in the nervous system of the body or in specific receptors in the brain to reduce the intensity of pain. Overdose deaths involving opioids, including prescription opioids, heroin, and synthetic opioids (like fentanyl), have increased by more than eight times since 1999. Overdoses involving opioids killed nearly 69,000 people in 2020, and over 82% of those deaths involved synthetic opioids. Therefore, it is imperative that new drugs be found that are not addictive and do not predispose patients to drug abuse.

The 5-HT₇R is the newest serotonin receptor to be identified and it has been shown to be involved in CNS conditions associated with unmet needs including neuropathic pain, depression, schizophrenia, anxiety, migraine, sleep disorders and the list goes on. The interest of our lab has been on CNS receptors as targets for drug design for many years but more recently our focus has shifted to the 5-HT₇R in particular, because of its potential to treat neuropathic pain and certain sleep disorders. In this presentation, we will discuss the design, synthesis, and the potential of functionally selective 5-HT₇ ligands as an alternative treatment for neuropathic pain and other CNS ailments

This work was financially supported by an NIH/NIGMS R16 grant number 1R16GM145581-01 and an NIGMS Endowment grant in support of an Eminent Scholar Chair in Biomedical Sciences to SYA. The research was also partly supported with funding from the U.S. Department of Education, Title III Part B, Strengthening Historically Black Graduate Institutions Programs (HBGI), awarded to Florida A&M University" and an RCMI grant # NIMHD U54 MD 007582.

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