A compound extracted from marine snail venom may be a potent alternative to opioids for pain relief, new research suggests.
Scientists at the University of Utah found that Rg1A, a compound isolated from the venom of Conus regius, a marine cone snail common in the Caribbean Sea, acts on a different pain pathway than those targeted by opioids.
“Rg1A4 works by an entirely new pathway, which opens the door for new opportunities to treat pain,” said J. Michael McIntosh, MD, study co-author and professor and director of research of psychiatry at the University of Utah in Salt Lake City, in a press release. “We feel that drugs that work by this pathway may reduce burden of opioid use.”
Prior research has suggested that antagonists of alpha9 alpha10 nicotinic acetylcholine receptors (nAChRs) might be a potential nonopioid target in the pathophysiology of chronic pain (Curr Pharm Des 2014;20:6042-6047). Rg1A is effective at blocking these receptors in rodents, but similar results have not been achieved in humans, according to the researchers.
They used synthetic chemistry to engineer 20 analogs of the compound to ensure they had one that would be effective in people. They found that the peptide Rg1A4 exhibited a “high potency for both human and rodent α9α10 nAChRs, and was at least 1,000-fold more selective for α9α10 nAChRs vs. all other molecular targets tested.”
The researchers tested the efficacy of this peptide by exposing rodents to a chemotherapy drug that causes extreme cold sensitivity and hypersensitivity to touch. They found that rodents that received Rg1A4—or were genetically engineered to not have this pain pathway—did not experience pain compared with those not given the compound.
Dr. McIntosh noted that even though the compound only remains in the body for about four hours, it “was still working 72 hours after the injection, still preventing pain.”
The lingering effect highlights this compound’s potential for preventing chronic pain from developing, and may be a treatment for patients with established pain who have run out of other options, according to the researchers.
Using marine snail venom to develop pain treatment is not a new concept. Researchers have had positive results using venom from another member of the Conoidea family (Integr Comp Biol 2016;56:962-972). The venom of the Conus magus marine snail has been used to develop ziconotide (Prialt, Jazz), which is used to treat chronic pain in HIV and cancer patients.
—Carina Elfving
Based on a press release from the University of Utah.