Researchers at the Washington University School of Medicine in St. Louis and Imperial College London have identified the site where the widely used anesthetic drug propofol binds to receptors in the brain to sedate patients during surgery. Until now, it has not been clear how propofol connects with brain cells to induce anesthesia. The researchers believe the findings, reported online on September 22, 2013 in the journal Nature Chemical Biology, eventually will lead to the development of more effective anesthetics with fewer side effects. "For many years, the mechanisms by which anesthetics act have remained elusive," explained co-principal investigator Alex S. Evers, M.D., the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University. "We knew that intravenous anesthetics, like propofol, act on an important receptor on brain cells called the GABAA receptor, but we didn't really know exactly where they bound to that receptor." Propofol is a short-acting anesthetic often used in patients having surgery. It wears off quickly and is less likely to cause nausea than many other anesthetics. But the drug isn't risk-free. Its potentially dangerous side effects include lowering blood pressure and interfering with breathing. In an attempt to understand how propofol induces anesthesia during surgery, scientists have 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 have altered the amino acids that make up the GABAA receptor in attempts to find propofol's binding site, but Dr. Evers said those methods couldn't identify the precise site with certainty.Login Or Register To Read Full Story