Theories of general anaesthetic action information
How drugs induce reversible suppression of consciousness
Structures of general anaesthetics widely used in medicine.[1] 1 - ethanol, 2 - chloroform, 3 - diethyl ether, 4 - fluroxene, 5 - halothane, 6 - methoxyflurane, 7 - enflurane, 8 - isoflurane, 9 - desflurane, 10 - sevoflurane
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 GABAA 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]
^ abcWeir, Cameron J. (2006). "The molecular mechanisms of general anaesthesia: dissecting the GABAA receptor". Continuing Education in Anaesthesia Critical Care & Pain. 6 (2): 49–53. doi:10.1093/bjaceaccp/mki068.
^Miller, Ronald D.; Cohen, Neal H.; Eriksson, Lars I.; Fleisher, Lee A.; Wiener-Kronish, Jeanine P.; Young, William L. (2014). Miller's Anesthesia (8th ed.). Philadelphia: Saunders. ISBN 978-0-7020-5283-5. OCLC 892338436.
^Egan, Talmage D. (2019). "Are opioids indispensable for general anaesthesia?". British Journal of Anaesthesia. 122 (6): e127–e135. doi:10.1016/j.bja.2019.02.018. PMID 31104756. S2CID 133023216.
^Urban, B. W. (2002). "Current assessment of targets and theories of anaesthesia". British Journal of Anaesthesia. 89 (1): 167–183. doi:10.1093/bja/aef165. PMID 12173228.
^ abFranks, Nicholas P. (2006). "Molecular targets underlying general anaesthesia". British Journal of Pharmacology. 147 (S1): S72–S81. doi:10.1038/sj.bjp.0706441. PMC 1760740. PMID 16402123.
^ abWeir, C. J.; Mitchell, S. J.; Lambert, J. J. (2017). "Role of GABAA receptor subtypes in the behavioural effects of intravenous general anaesthetics". British Journal of Anaesthesia. 119 (suppl_1): i167–i175. doi:10.1093/bja/aex369. PMID 29161398.
^ abDrexler, Berthold; Antkowiak, Bernd; Engin, Elif; Rudolph, Uwe (2011). "Identification and characterization of anesthetic targets by mouse molecular genetics approaches". Canadian Journal of Anesthesia. 58 (2): 178–190. doi:10.1007/s12630-010-9414-1. PMC 3330822. PMID 21174184.
^Maehle, Andreas-Holger (2009). "A binding question: the evolution of the receptor concept". Endeavour. 33 (4): 135–140. doi:10.1016/j.endeavour.2009.09.001. PMC 2812702. PMID 19837460.
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