Hunting for new anesthetics

Abstract

Existing anesthetics in clinical use have side effects that can make the drugs dangerous for vulnerable populations, such as the very young and the very old. These side effects include drops in blood pressure and inhibition of steroid biosynthesis. Anesthesiologists know how to mitigate those side effects, but drugs without them would be safer and easier to use. A team led by Edward J. Bertaccini of Stanford University School of Medicine and the VA Palo Alto Health Care System has identified a class of compounds that could lead to a new family of anesthetics without the side effects (Proc. Natl. Acad. Sci. U.S.A. 2019, DOI: 10.1073/pnas.1822076116). Through a series of modeling studies, one of which involved finding compounds that could bind strongly to the γ-aminobutyric acid (GABA) type A receptor, the researchers identified N-aryl pyrroles as a class of molecules to pursue. They searched compound databases for molecules with that