He was one of the researchers who discovered substances that provide effective pain relief without the addiction or sedative effects of the current drugs.
Researchers at FAU found that adrenaline receptors could be used to make highly effective analgesics.
The substances that activate adrenaline receptors instead of opioid receptors have the same pain-relieving effects as opiates but without their negative side effects such as respiratory depression and addiction. A team of international scientists led by the Chair for Pharmaceutical Chemistry at FAU carried out the research. The team’s findings, published in Science, an acclaimed scientific journal, represent a major milestone in the use and development of non-opioid pain relief methods.
Opiates cause addiction; new substances do not.
These drugs can be a lifesaver for people who are suffering from severe pain. They can cause serious side effects. In particular, morphine and opioids can cause nausea, dizziness, and constipation. Also, they can cause breathing problems, which may lead to respiratory failure. Opiates can also be addictive. Pain medications are responsible for a large part of the US drug epidemic.
Researchers from around the world are searching for alternatives to opioids to combat their adverse medical and social effects. Professor Dr. Peter Gmeiner, one of the researchers, is also involved. Gmeiner says, “We are focusing on receptors that dock onto pharmaceutical substances”. Only by understanding them at the atomic level will we be able to develop safe and efficient active substances.
Adrenaline receptors instead of opioid receptors: A new approach
Peter Gmeiner is following a promising path. “Many nonopioid receptors are involved in pain processing, but only a handful of these alternatives have yet to be validated as therapies”, says Gmeiner. Gmeiner and a team of researchers from Erlangen in Germany, China, Canada, and elsewhere have been focusing their attention on the alpha-2A receptor, a receptor that binds adrenaline. Some analgesics, including brimonidine and clonidine, as well as dexmedetomidine, already target this receptor. Gmeiner: Dexmedetomidine, a powerful sedative that relieves pain, is only appropriate for patients who are in intensive care.
The goal of the research consortium is to find a chemical compound that activates receptors in the central nervous system but has no sedative effects. Researchers searched through a virtual library of more than 300,000,000 molecules for compounds that were physically similar to receptors but chemically unrelated. Virtual docking simulations allowed the researchers to select around 50 molecules that would be tested and synthesized. Two of them met the criteria. The molecules were able to bond well, but they only activated a select group of signal pathways and subtypes of proteins. Dexmedetomidine responds to a wider range of proteins.
Pain relief in animals without sedation
Researchers optimized molecules using cryo-electron microscopes, which allowed them to synthesize agonists that had high concentrations in the brain. This reduced the pain sensation in animal models. Gmeiner says that “different tests have confirmed docking to the receptor is the cause of the analgesic effect.” We are particularly pleased that none cause sedation, even at the doses needed to relieve pain.
Separating analgesic from sedative properties represents a significant milestone in the manufacture and development of non-opioid medicines, especially as the newly discovered agonists are easy to produce and administer orally to patients. Professor Gmeiner has to dampen expectations for the rapid and widespread application of this drug in human medicine. “We’re still dealing with basic science.” The development of medication takes money and time. Both strict controls and significant funding are required. “These results are still very promising.”
