The unfolding story of how general anesthetics act

Abstract

Soon after Morton's 1846 demonstration of ether anesthesia, von Bibra and Harless proposed that ether acted by extracting brain lipids. This was followed by the influential theory of Meyer and Overton who proposed that anesthetics acted by directly perturbing membrane lipids. During the 1970s, evidence accumulated suggesting that this theory was wrong and the idea that anesthetics acted by directly binding to proteins began to take hold. This is now the accepted view and subsequent work focused on which proteins were important. There is now a consensus as to which proteins are important for intravenous anesthetics, but uncertainty still exists for the inhaled agents, although the anatomical target for these anesthetics in producing surgical immobility has been shown to be the spinal cord, rather than the brain.