Theories of general anaesthetic action

A general anaesthetic (or anesthetic) is a drug that brings about a reversible loss of consciousness.^[2] These drugs are generally administered by an anaesthetist/anesthesiologist to induce or maintain general anaesthesia to facilitate surgery.

General anaesthetics have been widely used in surgery since 1842 when Crawford Long for the first time administered diethyl ether to a patient and performed a painless operation. It has long been believed that general anaesthetics exert their effects (analgesia, unconsciousness, immobility)^[3] through a membrane mediated mechanism or by directly modulating the activity of membrane proteins in the neuronal membrane. In general, different anaesthetics exhibit different mechanisms of action such that there are numerous non-exclusionary molecular targets at all levels of integration within the central nervous system.^[4] However, for certain intravenous anaesthetics, such as propofol and etomidate, the main molecular target is believed to be GABA_A receptor, with particular β subunits playing a crucial role.^[5][6][7]

The concept of specific interactions between receptors and drugs first introduced by Paul Ehrlich in 1897^[8] states that drugs act only when they are bound to their targets (receptors).^[1] The identification of concrete molecular targets for general anaesthetics was made possible only with the modern development of molecular biology techniques for single amino acid mutations in proteins of genetically engineered mice.^[1][5][6][7]