At the turn of the 20th century, Meyer and Overton independently discovered the correlation between lipid solubility and anesthetic potency. Meyer concluded that all chemically indifferent, fat-soluble agents, would function as anesthetics. The presumed mechanism was related to the notion that the agents were able to act at the lipid bilayer of the cell membrane, particularly those of neurons. Later in the century, further experimentation showed that proteins were the likely site of action (perhaps ion channels or enzymes) by a study demonstrating a similar correlation between anesthetic potency and the ability to inhibit function of luciferase. Yet further studies found agents whose potency was not to the degree predicted by the Meyer-Overton hypothesis, suggesting it is not likely the case that lipid solubility is the primary determinant of potency.
Defined by: Will Corbett, MD