Researchers at Washington University School of Medicine in St. Louis and Imperial College London have identified the site where the widely used anesthetic（麻醉的） drug propofol（异丙酚） binds to receptors in the brain to sedate patients during surgery. Until now, it hasn't been clear how propofol connects with brain cells to induce anesthesia. The researchers believe the findings, reported online 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（难懂的）," explained co-principal investigator Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University. "We knew that intravenous（静脉内的） anesthetics, like propofol, act on an important receptor on brain cells called the GABA-A 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 (GABA-A) 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 GABA-A receptor in attempts to find propofol's binding site, but Evers said those methods couldn't identify the precise site with certainty.

"In previous work to directly identify anesthetic binding sites, GABA-A receptors had to be extracted from membranes and purified prior to performing the binding studies," he said. "Our method allowed us to study propofol binding to the intact receptor in its native membrane environment."