Using Anesthetics to Find Drugs

An inter-disciplinary team from the University of Pennsylvania and the University of Wisconsin, comprised of chemists and anesthesiologists, has devised a new model of discovering how anesthetics spread through the human body when people “go under.” The new technique makes use of a fluorescent compound, which is able to “light up” the areas it influences, in very much the same way an fMRI machine discovers activated portions of the brain.

With the innovation, anesthesiologists worldwide will be able to test new drugs faster and more effectively in the end, and to also reduce the number of people suffering accidents under the knife. Details of the finds are published in a recent online issue of the scientific journal Proceedings of the National Academy of Sciences (PNAS).

According to the paper, the fluorescing compound 1-aminoanthracene, also known as 1-AMA, will give experts the possibility to look for new molecules for their drugs to target and also to increase the effectiveness of the overall procedure.

Over the last few years, a lack of knowledge on what the anesthetics were actually doing inside the human body hindered research in the field, but with the help of the new high-throughput assay, advancements in this area may now be possible. The first tests were conducted on transparent tadpoles, which were sedated and then injected with 1-AMA. Because the animals were see-through, the researchers could image the action of the anesthetic in the creatures' brain, with the help of the fluorescent molecule.

“We don't know much about how anesthetics work at a molecular level. Thus, the development of new anesthetics has become a stagnant field. This new tool will allow for the high-throughput screening of novel drugs,” Penn School of Medicine Austin Lamont Professor of Anesthesiology and Critical Care Roderic G. Eckenhoff, who is also the vice-chairman of research at the institution, explained.

“1-AMA appears to be specific in its binding to proteins and also in its in vivo localization, which should give us the opportunity to determine its mechanism of action. We hope to be able to extend our findings to learn how current general anesthetics, such as propofol, work in human patients. There are many different and challenging aspects of trying to learn how anesthetics work that involve medicinal chemistry, biochemistry, molecular modeling, imaging, cell electrophysiology, pharmacology, neurobiology and animal physiology,” Penn Department of Chemistry Assistant Professor Ivan J. Dmochowski added.