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Breakthrough Propofol Study May Lead To Better Anesthetics

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Breakthrough Propofol Study May Lead To Better Anesthetics

Post by Admin on Mon Sep 23, 2013 9:08 pm

Breakthrough Propofol Study May Lead To Better Anesthetics
by Brett Smith for redOrbit.com – Your Universe Online


New research from an international team of scientists has revealed the specific chemical mechanism behind the anesthetic propofol, the drug widely known for being implicated in the death of music icon Michael Jackson.

According to a report published in the journal Nature Chemical Biology, the international team located the specific site on the brain where propofol binds to receptors and sedates patients before surgery.

“For many years, the mechanisms by which anesthetics act have remained elusive,” explained co-author Dr. Alex S. Evers, head of the anesthesiology department 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.”

Used on patients just before surgery, propofol wears off rapidly and is less likely to cause nausea than many other anesthetics. The drug has a few potentially hazardous side effects, however, such as lowering blood pressure and breathing disruption.

Scientists have known that the drug interacts with gamma-aminobutyric acid type A (GABAA) receptors on brain cells and past research has focused on altering the receptors’ chemical makeup in an attempt to locate propofol’s binding site.

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

In the new study, scientists engineered a molecule that closely models the structure and function of propofol but has an additional chemical group that permanently fixes to its binding site on the GABAA receptor when exposed to a certain wavelength of light.

“Normally, an anesthetic drug binds to the GABAA receptor transiently,” explained study author Nicholas P. Franks, PhD, professor of biophysics and anesthetics at Imperial College London. “But for the purposes of this research, we wanted to create an analogue that behaved exactly like propofol except that we could activate this chemical hook to permanently bind the drug to the receptor.”

After this permanent binding, the team extracted the receptor, cut it up and identified the location on the protein that the propofol model was attached to.

“This was the tricky step that the Evers group at Washington University had perfected,” Franks said.

The researchers said the techniques developed in this study could be useful for identifying the binding sites of other anesthetics. They said their method also can be used to learn about the specific mechanisms behind other types of substances, including psychiatric agents and anti-seizure drugs.

“Whilst propofol is the best anesthetic we have today, it is important for patient safety that we come up with new versions of the drug that work just as well or better as anesthetics, but have fewer or less dangerous side effects,” Franks said.

Propofol is considered an extremely powerful sedative and a controlled substance. At the time of Michael Jackson’s death, he had been administered the drug along with lorazepam, another sedative, and midazolam, which is used to treat insomnia.

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Personal note: Being that I am a med pro-I find this refreshing and had hoped this would happen. It is so sad that MJ is why the study was implemented but he did inspire good work to be done which likely will result in lives saved.

L.O.V.E. you Michael!

Michael Jackson transcended our imaginations and continues to uplift our souls and spirits through his tremendously meaningful life well lived.

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