Mechanisms of action of general anesthetics

Since William Morton successfully demonstrated the use of inhaled ether for surgical anesthesia in 1846, the development of new anesthetics and safe general anesthesia techniques have contributed greatly to the advancement of surgery and other invasive procedures. However, the underlying neurocellular mechanisms by which the state of general anesthesia is achieved are only just beginning to be understood. The general anesthetic state comprises multiple components (amnesia, unconsciousness, analgesia, and immobility), each of which is mediated by effects on different neurotransmitter receptors and neuronal pathways. In this review, we focus on the mechanisms of action of inhaled and intravenous anesthetics, and we describe the neuronal systems thought to be involved in mediating the clinically relevant actions of general anesthetics. We then describe the neurotransmitter receptors that are the principal targets of many general anesthetics, in particular ã-aminobutyric acid type A receptor subtypes.