Theories of General Anaesthetic Action

Theories Of General Anaesthetic Action

A general anaesthetic (or anesthetic) is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthetist/anaesthesiologist in order 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 always been believed that general anaesthetics exert their effects (analgesia, amnesia, immobility) by modulating the activity of membrane proteins in the neuronal membrane. However, the exact location and mechanism of this action are still largely unknown although much research has been done in this area. There are a number of outdated and modern theories that attempt to explain anaesthetic action.

The concept of specific interactions between receptors and drugs first introduced by Paul Ehrlich states that drugs act only when they are bound to their targets (receptors). However, this concept is not working well in case of general anaesthetics because:

• Molecular structures of general anaesthetics widely used in medicine are very simple and diverse so that there is no obvious structure–activity relationship (see structures of general anaesthetics widely used in medicine: 1-ethanol, 2- chloroform, 3-diethylether, 4-fluroxene, 5-halothane, 6-metheoxyflurane, 7- enflurane, 8-isoflurane, 9-desflurane, 10-sevoflurane)
• Most general anaesthetics have remarkably weak affinity for their targets acting at much higher concentrations than most other drugs so that diverse side effects are inevitable .

All these common features of general anaesthetics made it hard for early researchers to believe that general anaesthetics act in a specific manner and their action on neuronal membrane was thought to be global (through nonspecific perturbation of lipid membrane of CNS neurons) rather than through specific sites.