Membrane-mediated anesthesia

Membrane-mediated anesthesia or anaesthesia (UK) is a mechanism of action that involves an anesthetic agent exerting its pharmaceutical effects primarily through interaction with the lipid bilayer membrane.

The relationship between volatile (inhalable) general anesthetics and the cellular lipid membrane has been well established since around 1900, based on the Meyer-Overton Correlation.

[1][2][3][4][5] Since 1900 there have been extensive research efforts to characterize these membrane-mediated effects of anesthesia, leading to many theories but few answers.

It originally compared the anesthetic partition coefficient in olive oil (X-axis) to the effective dose that induced anesthesia in 50% (i.e., EC50) of the tadpole research subjects (Y-axis).

[1][2][3][4] Modern renditions of the Meyer-Overton plot usually compare olive oil partition coefficient of the Inhalational or Intravenous drug (X-axis) to the minimum alveolar concentration (MAC) or the effective dose 50 (i.e., ED50) of the anesthetic agent (Y-axis).

[20][21][citation needed] This is the first hypothesis to explain the correlations of anesthetic potency with lipid bilayer structural characteristics, describing both mechanistic and thermodynamic rationale for the effects of general anesthesia.

[citation needed] Inhaled anesthetics partition into the membrane and disrupt the function of ordered lipids.

The anesthetics hydroxychloroquine, tetracaine, and lidocaine blocked entry of palmitoylated protein into the endocytic pathway.

[27] More than 100 years ago, a unifying theory of anesthesia was proposed based on the oil partition coefficient.

Nonetheless, several of the early conceptual ideas about how disruption of lipid partitioning could affect an ion channel have merit.