Non-opioid compounds squelch pain without sedation: New molecules are lead candidates for alternative to narcotics, say researchers

A newly identified set of molecules alleviated pain in mice while avoiding the sedating affect that limits the use of opiates, according to a new study led by researchers at UC San Francisco. The molecules act on the same receptor as clonidine and dexmedetomidine — drugs commonly used in hospitals as sedatives — but are chemically unrelated to them and may not be addictive.

Clonidine and dexmedetomidine are also both effective pain killers but so sedating that they are rarely used for pain relief outside of the hospital.

“We showed that it’s possible to separate the analgesic and sedative effects related to this receptor, said Brian Shoichet, PhD, professor in the School of Pharmacy, and one of four senior authors of the study, which appears in the Sept. 30, 2022, issue of Science. “That makes it a very promising target for drug development.”

The research is part of a five-year grant from the Defense Advanced Research Projects Agency (DARPA), and began shortly before the COVID-19 pandemic, with the aim of finding effective painkillers that can be used together or in conjunction with opioids.

The work brings together researchers from a variety of disciplines; Shoichet’s co-authors include UCSF anatomy chair Allan Basbaum, PhD, chemist Peter Gmeiner of Freidrichs Alexander University in Germany, structural biologist Yang Du, PhD, of the Chinese University of Hong Kong, and molecular biologist Michel Bouvier, PhD, of the University of Montreal.

“Together, we were able to take this from the most fundamental level to identifying new molecules that might be relevant, and then to demonstrating that, in fact, they are relevant,” said Basbaum. “That doesn’t happen very often.”

6 Molecules Out of 300 Million

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