The importance of inhaled anesthetics was dramatically demonstrated by Morton 142 years ago. Since that time the ability to render the patient insensitive to pain has permitted sophisticated, life-saving surgical procedures. Although millions of patients in the United States are subjected to inhalation anesthesia each year, no explanation can be given as to how these compounds act on the brain. A better understanding of the mechanism of anesthetic action can contribute to the design of more suitable anesthetics or point to the use of selected combinations of compounds. Recent advances in the molecular mechanisms of anesthesia have focused attention on membrane proteins as the targets of anesthetic action. Neurophysiological evidence suggests that synaptic proteins are involved. The hypothesis that anesthetics act directly on synaptic proteins is attractive, but requires experimental support. If this hypothesis is correct, one can expect to observe specific binding of inhalation anesthetics to synaptic receptors. Significant functional changes in the receptor are expected to correlate with this binding interaction at a concentration range relevant to clinical anesthesia. Clinical observations on the effects of anesthetic adjuvants and temperature dependence of anesthetic requirement are important clues in identifying the target site of action and in the formulation of a molecular mechanism. The effect of temperature on anesthetic-receptor interaction can be used to test the protein-binding model. Recent biochemical and molecular biological advances in the study of acetylcholine receptors have made possible an unique opportunity to examine the action of inhaled anesthetics. For the first time, a synaptic receptor is sufficiently understood to serve as a model for studying inhaled anesthetics. Technical advances also allow sufficient quantities of purified acetylcholine receptors to be used for studying the action of inhaled anesthetic under controlled biochemical conditions. The existence of a large number of genes coding for neuronal acetylcholine receptors and the presence of these receptors throughout the brain suggest that the acetylcholine receptor is one of the major excitatory systems in the brain and may be the target site of anesthetic action.
