New oral painkiller developed for chronic abdominal pain

The University of QueenslandNov 18 2024

University of Queensland researchers have developed a new class of oral painkillers to suppress chronic abdominal pain that is based on the peptide hormone oxytocin that drives childbirth contractions.

Associate Professor Markus Muttenthaler from UQ's Institute for Molecular Bioscience led a team that has changed the chemical structure of oxytocin to make it gut-stable after earlier work revealed the hormone could treat abdominal pain.

Dr. Muttenthaler said there was an urgent need for new treatments for the chronic pain caused by gastrointestinal disorders such as irritable bowel syndrome (IBS) and irritable bowel diseases (IBD).

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.

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."

Dr. Markus Muttenthaler, Associate Professor from UQ's Institute for Molecular Bioscience 

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."

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."

The research is published in Angewandte Chemie.