Substances that activate adrenaline receptors as opposed to opioid receptors have similar pain-relieving properties to opioids minus the negative side effects. The corresponding study was published in Science.
Opioids are effective at relieving pain. However, they come with severe side effects, including addction and respiratory failure. That said, researchers are keen to find alternative ways to treat pain- whether chronic or acute.
While many non-opioid receptors are involved in pain processing, very few have been validated for therapeutic use. As such, in the present study, researchers focused on the alpha 2A adrenergic receptor- a receptor that binds with adrenaline. Some analgesics already target this receptor, such as dexmedetomidine. However, its strong sedative effect limits its use to hospital settings.
This in mind, the researchers searched a virtual library of over 300 million molecules to find chemicals that activate the receptor in the central nervous system without inducing a sedative effect. In the end, they selected around 50 molecules for synthesis and testing.
From tests, they noted that the molecules had good bonding characteristics and activated very selective cellular signaling pathways, differentiating them from dexmedetomidine, which responds to a wider range of proteins.
The researchers then optimized the molecules and synthesized agonists that produced high concentrations in the brain and reduced pain in animal models.
"Various tests confirmed that docking on the receptor was responsible for the analgesic effect," explained Prof. Dr. Peter Gmeiner, Chair of Pharmaceutical Chemistry at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), lead author of the study, "We are particularly pleased about the fact that none of the new compounds caused sedation, even at considerably higher doses than those that would be required for pain relief."
While the research is a milestone for creating a non-opioid pain medication, Prof. Gmeiner noted that they are still in the very early stages of research and that much further study is needed before the experimental drugs may be tested in humans.
Sources: Science, Science Daily