Correlating the clinical actions and molecular mechanisms of general anesthetics.
OBJECTIVE
To summarize recent in-vitro and in-vivo research on molecular mechanisms of general anesthetics' actions.


RESULTS
Classes of general anesthetics with distinct clinical profiles appear to induce amnesia, hypnosis, and immobility via different molecular targets. Propofol, etomidate, and barbiturates produce profound amnesia and hypnosis, but weak immobility, by enhancing the activity of specific gamma-aminobutyric acid typeA receptors. In contrast, nitrous oxide, xenon, and ketamine produce analgesia, but weak hypnosis and amnesia, by inhibiting glutamate and nicotinic receptors and activating potassium 'leak' channels such as TREK-1. Volatile halogenated anesthetics show little selectivity for molecular targets. They act on all the channels mentioned above, and other targets such as glycine receptors and mediators of neurotransmitter release.


CONCLUSIONS
Several clinically distinct 'anesthetic states' are induced by different classes of drugs acting on neuronal circuits via different molecular targets. Understanding the mechanisms underlying the therapeutic and toxic actions of general anesthetics helps us reframe the 'art' of anesthesia into more of a 'science'. These studies also enhance efforts to develop new drugs with improved clinical utility.
Solt
Ken
K
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA.
Forman
Stuart A
SA
D000777:Anesthetics / Q000145:classification / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D011485:Protein Binding; D018079:Receptors, GABA / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
D000777:Anesthetics; D007473:Ion Channels; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate