Singapore researchers discover potential new drug to treat depression with fewer side effects

SINGAPORE: Researchers at the National University of Singapore (NUS) have made significant strides towards developing drugs that treat conditions like depression and anxiety with fewer side effects.

Led by Professor Gavin Dawe, Head of the Department of Pharmacology at NUS Medicine, the team focused on modifying relaxin-3, a neuropeptide predominantly found in the human brain and nervous system.

The research, published in Science Signaling, delves into the intricate workings of relaxin-3, which regulates various physiological functions such as stress responses, appetite, mood, and pain perception.

The challenge lies in the fact that when relaxin-3 interacts with its target receptor RXFP3, it triggers multiple signalling responses, affecting diverse physiological processes.

Recognizing the issue of unwanted side effects arising from the activation of different RXFP3 signalling pathways, the team embarked on a mission to selectively activate specific functions.

Their breakthrough discovery involves modifying relaxin-3 molecules to activate only a portion of the RXFP3 response, a mechanism termed biased agonism.

Prof Dawe expressed the significance of their findings, saying, “Our study has pointed to potential ways of developing drugs by modifying relaxin-3, or other neuropeptides, that can selectively activate specific functions within the body.”

This selective activation could pave the way for drugs designed to have more specific effects, reducing undesired side effects and enhancing their effectiveness in managing conditions like anxiety, depression, eating disorders, obesity, and addiction.

Dr Tharindunee Jayakody, the study’s first author and a PhD alumna of the Department of Pharmacology at NUS Medicine, emphasized that while they are in the early stages of developing clinically useful drugs, the promising findings mark a significant step forward.

This collaborative effort holds promise for the future of mental health treatments, offering hope for more targeted and effective medications with fewer side effects.

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