KEY POINTS

1. The structural diversity of inhaled anesthetics suggests that they all do not interact directly with a single, specific receptor site.
2. Any molecular hypothesis of anesthesia must explain the effects of anesthetics on the whole organism. Physical or biochemical changes important to the

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   mechanism of anesthesia must occur within seconds of anesthetic administration and be rapidly reversible on removal of the anesthetic.
3. Potencies of inhaled anesthetics depend on the end point measured. The best-characterized measurement of anesthetic potency is MAC, the minimum alveolar concentration of an agent that produces immobility in 50% of subjects exposed to a noxious stimulus.
4. Inhaled anesthetics have presynaptic and postsynaptic effects in the brain and spinal cord. The ability of anesthetics to prevent a motor response to noxious stimulation results from a site of action in the spinal cord.
5. Many excitatory and inhibitory neurotransmitters and their receptors have an influence on the anesthetic requirement. However, the predominant effects of inhaled anesthetics cannot be explained by the depletion, production, or release of a single neuromodulator in the CNS.
6. The Meyer-Overton rule describes the correlation between lipid solubility and anesthetic potency. Because of this correlation, the search for the molecular bases of anesthetic action has often focused on cellular hydrophobic regions.
7. Clinical concentrations of inhaled anesthetics (i.e., about one anesthetic molecule for every 80 membrane phospholipid molecules) produce only modest changes in membrane lipid structure and function.
8. The Meyer-Overton rule is imperfect, and many exceptions exist. Nonimmobilizers are lipid soluble compounds that fail to produce immobility in response to a noxious stimulus but do impair learning and memory.
9. The ultimate action of inhaled anesthetics is on specific neuronal membrane proteins that permit the translocation of ions during membrane excitation. Although this probably occurs by a direct binding of anesthetics to membrane protein channels or their surrounding lipids, or both, the possibility remains that inhaled anesthetics act indirectly through production of a second messenger.
10. The ability of inhaled anesthetics to modulate ion flow through neurotransmitter receptor-channel complexes can be markedly altered by selective single amino acid mutations in protein channels. These critical amino acids may form the specific binding sites for inhaled anesthetics.