A new alternative to opioids has emerged from an unlikely place.
Scientists at the University of Utah have found a compound in Conus regius, a small marine cone snail common to the Caribbean Sea, that blocks pain by targeting a pathway not associated with opioids.
In the study, researchers found that a compound isolated from the snail’s venom—Rg1A—acts on a pain pathway distinct from that targeted by opioid drugs.
The scientists used rodent models to show that a9a10 nicotinic acetylcholine receptors (nAChR) function as a pain pathway receptor and that RglA4 is an effective compound to block this receptor.
The pathway adds to a small number of non-opioid-based pathways that could be further developed to treat chronic pain.
The compound is able to work its way through the body in four hours, but the scientists found the beneficial effects lingered.
“We found that the compound was still working 72 hours after the injection, still preventing pain,” Michael McIntosh, professor of psychiatry at the University of Utah Health Sciences, said in a statement. “What is particularly exciting about these results is the aspect of prevention.
“Once chronic pain has developed, it is difficult to treat,” he added. “This compound offers a potential new pathway to prevent chronic pain from developing in the first place and also offers a new therapy to patients with established pain who have run out of options.”
In previous research, scientists showed that RgIA was effective in rodents, but the scientists wanted to ensure they had a compound that would work in humans.
To test this, the research team used synthetic chemistry to engineer 20 analogs of the compound and found that the analog RgIA4 was tightly bound to the human receptor.
They then tested whether the compound relieved plan by administering it to rodents that were exposed to a chemotherapy drug that causes extreme cold sensitivity, as well as hypersensitivity to touch.
“Interactions that are not normally painful, like sheets rubbing against the body or pants against the leg, becomes painful,” McIntosh said. “We feel that drugs that work by this pathway may reduce burden of opioid use.”
While the untreated rodents experienced pain after exposure to the drug, the rodents given the compound did not experience pain.
This demonstrated that a9a10 nAChR acts as a pain pathway receptor and that RgIA4 prevents the receptor from being activated.
“RgIA4 works by an entirely new pathway, which opens the door for new opportunities to treat pain,” McIntosh said.
The research team plans on continuing pre-clinical testing to investigate the safety and effectiveness of the new drug therapy.
According to the Centers for Disease Control and Prevention, 91 Americans die every day from an opioid overdose.
Filed Under: Drug Discovery