A team of scientists led by chemists Stephen Martin and James Sahn from the University of Texas at Austin have discovered what they say is a powerful painkiller that works on a previously unknown pain pathway. The synthetic compound, known as UKH-1114, is as effective in relieving neuropathic pain in injured mice as a widely used pain relief drug called gabapentin, but it works at a much lower dose. with a longer duration of action.
If researchers can demonstrate that the drug is safe, effective and non-addictive in humans – a process that typically takes years – the discovery could be key to addressing one of today’s biggest public health challenges. : the epidemic of opioid abuse.
Almost a third of Americans suffer from chronic pain, but the most effective pain relievers – opioids – are addictive and often require an increased dose to maintain their effectiveness. According to the National Institute on Drug Abuse, approximately 2 million people in the United States are addicted to prescription opioid painkillers. Alternatives to opioids have their own downsides – for example, gabapentin (sold as Neurontin) can cause cognitive impairment in some people.
“This opens the door to a new treatment for neuropathic pain that is not an opioid,” said Martin, Professor and M. June and J. Virgil Wagoner Regents Chair in Chemistry. “And that has huge implications.”
The painkiller they found binds to a receptor on central nervous system cells called the sigma 2 receptor. Although it was discovered 25 years ago, scientists still didn’t know what sigma 2 did until ‘now.
Theodore Price, an associate professor of neuroscience at the University of Texas at Dallas and a leading chronic pain expert, tested UKH-1114 on mice with nerve damage and found it relieved pain as well as pain. gabapentin, but at a much lower dose (one-sixth more) and was effective for much longer (lasting a few days, versus 4-6 hours). This research is the first to demonstrate that the sigma 2 receptor can be a target for the treatment of neuropathic pain.
The results are published in the August 18 print edition of the journal. ACS Chemistry Neurosciences. An earlier article, published online May 28 in the journal Proceedings of the National Academy of Sciencesdescribed the molecular cloning and identification of the sigma 2 receptor.
The researchers have filed patent applications on the new compound.
Neuropathic pain, or chronic pain, is caused when nerves in the central nervous system are damaged. It can result from, among other things, chemotherapy, diabetes, and injuries to the brain or spinal cord.
There is still a lot of work to do before the UKH-1114 can enter the market. Further studies are needed to demonstrate safety, efficacy and oral bioavailability. In the meantime, scientists are struggling to understand, at a fundamental level, how activation of the sigma 2 receptor relieves neuropathic pain.
Still, Martin and Sahn are excited about the compelling results from the mouse model.
“We started working on basic chemistry in the lab,” said Sahn, a researcher in the Department of Chemistry. “But now we see the possibility that our discoveries could improve people’s quality of life. It’s very satisfying.”
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