An international team of science and anesthesiology researchers recently discovered the specific chemical mechanism that makes propofol such a successful anesthetic. Through their research, they were able to identify the site where this anesthetic binds to brain receptors, sedating patients for surgical procedures. Although propofol is one of the most popular anesthetics, anesthesiologists and scientists have been unsure of how the drug connects with brain receptors to induce anesthesia. The findings from this study were reported in Nature Chemical Biology, an online journal. According to researchers involved in this new anesthesiology research, they hope that these recent findings will lead to new anesthetics in the future, particularly anesthetics that have fewer side effects.
Anesthesiologists often prefer propofol as an anesthetic because patients are less likely to experience nausea. Propofol also wears off quickly after surgery another benefit that makes it a popular choice today. Of course, this drug still has several side effects, such as breathing disruption and the potential to lower blood pressure, and both of these side effects have the potential to be hazardous to patients.
Although the medical field has known that intravenous anesthetics, including propofol, work on GABAA (Gamma-Aminobutyric Acid type A) receptors, it has been unclear where these anesthetics bind to the GABAA receptor. In the past, researchers have worked to alter the chemical makeup of GABAA receptors, working to try to identify the binding site. However, past studies were ineffective. This new propofol study studies GABAA receptors in their native environment, which allowed researchers to find specifically where propofol binding takes place.
In this study, scientists took a molecule that closely resembled the function and structure of propofol and engineered it to attach permanently to a binding site after being exposed to a particular light wavelength. Once the molecule was bonded to the GABBA receptor, researchers were able to cut it up and then identify the specific location the model attached to. Not only did this technique help in the study of propofol, but researchers believe that these techniques may prove helpful for studying other anesthetics to find their unique binding sites.
According to Nicholas P. Franks, PhD, Imperial College professor of anesthetics and biophysics, “”Normally, an anesthetic drug binds to the GABAA receptor transiently. 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. The next step was then to extract the receptor, cut it into pieces and identify the precise piece of the protein where the propofol analogue had attached to the receptor. This was the tricky step that the Evers group at Washington University had perfected.”
This new technique, perfected by Franks and Alex S. Evers, MD, co-principal investigator in this study and Washington University’s Department of Anesthesiology Head, may have implications that go far beyond just propofol. These new techniques may help lead to the development of new anesthetics that provide the benefits of anesthesia without the side effects. Franks noted, “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”
BIO: Joy Burgess is a full-time freelance writer with more than 12 years of writing experience. For more than six years, she has specialized in medical writing, drawing upon her previous medical experience in emergency care, private home health care and geriatric care.
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