Pain Relief Without Addiction: Researchers Develop New Oxytocin-Based Oral Drug

Researchers have developed a new type of oral painkiller for chronic abdominal pain, inspired by the peptide hormone oxytocin, which is known for triggering contractions during childbirth.

Researchers at the University of Queensland have developed a new type of oral painkiller designed to relieve chronic abdominal pain, based on a modified form of the hormone oxytocin, best known for its role in childbirth contractions.

Led by Associate Professor Markus Muttenthaler from UQ’s Institute for Molecular Bioscience, the team altered the chemical structure of oxytocin to make it stable in the digestive system. This breakthrough builds on earlier findings that oxytocin can help alleviate abdominal pain.

Dr. Muttenthaler emphasized the urgent need for better treatments for chronic gastrointestinal pain, particularly in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).

Gut-Stable Peptides: A New Frontier

“This pain affects up to 15 per cent of adults in their lifetime, and all we have are anti-inflammatories and opioids which can cause side effects and addiction,” Dr. Muttenthaler said. “Our research focuses on peptides that are highly potent and selective molecules and have few side effects. However, nearly all peptide drugs must be injected as they are rapidly digested in the gut. We have now developed a way of making peptides gut-stable so they can be given orally. This is a new and highly promising approach to treating gut disorders.”

Oxytocin is a peptide hormone produced in the brain which is known as the ‘bonding hormone’ or the ‘love molecule’ due to its effects on relationship building, empathy, and trust. Oxytocin is also the key hormone that induces uterine contractions during labour and facilitates milk release during breastfeeding.

“We identified the parts of oxytocin that are rapidly broken down by gut enzymes and used medicinal chemistry to render them gut-stable while ensuring that the new molecule was still able to activate the oxytocin receptor,” Dr. Muttenthaler said. “We now have a new class of molecules that are potently active but do not degrade in the stomach or intestine, meaning they can be taken orally.”

Targeted Action, Fewer Side Effects

The research indicates that the new molecules work in the colon and do not need to cross the gut barrier into the bloodstream to suppress abdominal pain.

“This is a very safe therapeutic approach as it reduces the risk of side effects in the rest of the body, a problem with many other systemic drugs,” Dr. Muttenthaler said. “This is an exciting new mode of action to prevent pain. We are currently looking for investors to accelerate pre-clinical studies, with the goal of taking it into the clinic. Now that we have perfected making peptides stable, we are looking at other gut drugs to improve treatment options for gastrointestinal disorders, an unmet medical need.”

Reference: “Oxytocin Analogues for the Oral Treatment of Abdominal Pain” by Thomas Kremsmayr, Gudrun Schober, Matthias Kaltenböck, Bradley L. Hoare, Stuart M. Brierley and Markus Muttenthaler, 9 October 2024, Angewandte Chemie International Edition.
DOI: 10.1002/anie.202415333

Funding: European Research Council, Australian Research Council, Vienna Science and Technology Fund, Austrian Academy of Sciences, National Health and Medical Research Council

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