Early in the 20th century, Sowton and Sherrington identified the synapse as a likely target of general anesthetic action (1). Brooks and Eccles (2) and Bremer and Bonnet (3) later demonstrated depression of synaptic transmission in the central nervous system (CNS), by concentrations of general anesthetics that did not affect axonal conduction. Larrabee and Pasternak (4) showed that impulse conduction in myelinated and unmyelinated axons of the autonomic nervous system was resistant to a variety of intravenous and volatile anesthetics, whereas excitatory synaptic transmission was significantly suppressed. This important paper firmly established the synapse as a major site of action of general anesthetics.