Treating Neurological Disorders Caused by Opioid Addiction – Targeting the µ Opioid Receptor

Yan Zhang, PhD, Professor, Department of Medicinal Chemistry, Virginia Commonwealth University, a recognized expert in the study of drug design and development to treat various types of diseases, has developed novel compounds to treat neurological disorders related to opioid addiction.

Drug use disorder is a growing global epidemic. In 2018, over 72,000 people died in the US alone from opioid overdose. The two current methods for treating opioid addiction include detoxification and maintenance therapy using opioid receptor antagonists, such as naloxone and naltrexone. While effective, naloxone and naltrexone have the potential to cause hepatotoxicity, cardiovascular and pulmonary problems at higher doses.

The analgesic function and addiction/abuse liability of many clinically available opiates are due to their interaction with the µ opioid receptor (MOR). A number of MOR selective antagonists and partial agonists have been used for the treatment of opioid abuse and addiction.

Dr. Zhang has designed and synthesized a number of highly selective and potent opioid antagonists. The first compound identified as a peripherally selective MOR antagonist, NAP. Since NAP’s discovery, generations of new compounds have been studied; NAQ, NAN, and NFP. In vitro competition assays showed that NAQ, NAN, and NFP have superior selectivity for the MOR over existing compounds. In vivo withdrawal studies showed that NAQ, NAN, and NFP produced significantly less withdrawal symptoms compared to naloxone at similar doses. The findings suggest that these compounds may serve as a lead compound to develop novel dual selective ligands for treating opioid addiction and abuse.

The technology

Pharmacology Data Summary

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