TOWARDS AN UNDERSTANDING OF THE MECHANISM OF ANAESTHESIA

The structural diversity of anaesthetic compounds suggests that anaesthetics do not act at a single specific receptor. However, the close correlation between the lipid solubility of anaesthetics and their potencies (Meyer‐Overton rule) does imply a common mechanism: A Unitary Hypothesis. Anaesthetizing Partial E'ressure x oil/gas part. coef. varies only 2 x over a range of 70,000 in partial pressures. This suggests that a specific number of anaesthetic molecules occupy a crucial hydrophobic site in the CNS, but the MeyerOverton rule offers no mechanistic explanation for its validity. The putative site of action of anaesthetics is the synapse because the relative resistance of larger axons to anaesthetic induced depression narrows the site of hydrophobic action to synapic regions or axons with small diameter at the nerve terminal (Richards, 1981) (see Figure 1).