A more subtle approach could be the key to reducing damage from heart attacks, or even stopping them in their tracks.

A cross-fields project has brought together researchers from the worlds of molecular pharmacology and medicinal chemistry, to create a powerful new weapon for heart health.

An ongoing project has already shown insights into a specific protein belonging to the family of G protein-coupled receptors (GPCRs). After successfully combining two molecules, the team is a step closer to creating a brand new class of drugs that are better targeted and with fewer side effects.

Current GPCR drugs work either by fully activating or completely blocking receptors, treating the proteins like a simple ‘on-off’ switch. The latest research has discovered alternative recognition sites on GPCRs that can be targeted by drugs to fine-tune the behaviour of the protein, turning the on-off switch into a dimmer control.

Also, many current drugs which target the GPCR adenosine A1 receptor also slow down the heart, and too much activation can stop the heart.

“Correct dosage has been a serious challenge in clinical trials for A1 receptor drugs. The consequences are serious; a dosage that is too high can stop the heart from beating. Too low, and the drug fails to prevent cell damage. Getting this balance right has been a big problem,” Professor Peter Scammells, from the Monash Institute of Pharmaceutical Sciences (MIPS) said.

Professor Arthur Christopoulos, also from MIPS, said the study focused on finding new ways to activate the protein, to achieve the beneficial effects (protection) without the side effects (slowing the heart).

“We turned to our knowledge of alternative recognition sites on the A1 receptor and specifically designed a new class of molecule that contained two active components linked together, one binding to the main site on the receptor for activation, and another binding to the alternative site for fine-tuning of the activity. Our ‘dimmer switch’ strategy worked, resulting in a molecule that protected heart cells but did not affect heart rate at all – at least in our animal models,” Professor Christopoulos said.

“The beauty of this protein is that if you activate it effectively, you minimise the heart attack and protect the heart cells, and that’s something that’s never been done before.”

The findings will inform the next phase of the research, hoping to develop a new drug for future trials.

The Monash University research was published today in the journal Proceedings of the National Academy of Sciences, USA.