Drug that killed MJ set to help in development of new anaesthetics
Washington: Researchers have identified the site where the widely used anesthetic drug propofol binds to receptors in the brain to sedate patients during surgery, and this could lead to the development of new and better anaesthetics.
Co-principal investigator Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University, said that for many years, the mechanisms by which anaesthetics act have remained elusive.
In an attempt to understand how propofol induces anesthesia during surgery, scientists tried to identify its binding site within the gamma-aminobutyric acid type A (GABAA) receptor on brain cells. Activating these receptors - with propofol, for example - depresses a cell's activity.
Researchers altered the amino acids that make up the GABAA receptor in attempts to find propofol's binding site, but Evers said those methods couldn't identify the precise site with certainty.
Evers' lab teamed up with a group at Imperial College that had been taking the same approach. Led by Nicholas P. Franks, PhD, professor of biophysics and anaesthetics, the group has spent years creating a photoanalogue of propofol that both behaves in precisely the same way as propofol and contains a labeling group that permanently attaches to its binding site on the GABAA receptor when exposed to a specific wavelength of light.
In creating the analogue of propofol, it's as if the researchers put a tiny hook onto the molecule so that when it binds to the GABAA receptor, it grabs onto the receptor and won't let go.
The findings have been published in the journal Nature Chemical Biology.
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