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Purpose of Review: To summarize recent in-vitro and in-vivo research on molecular mechanisms of general anesthetics' actions., Recent Findings: 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., Summary: 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.

A recent lack of availability of the anesthetic agent methohexital in the United States allowed for a naturalistic study of the efficacy and the adverse effects of alternatives. Methohexital, propofol, and thiopental were compared as anesthetic agents for electroconvulsive therapy in 95 patients treated during a 23-month period in a general public hospital. Missed seizures and arrhythmias were infrequently observed (<4% for any agent). Methohexital was found significantly related to longer seizure durations in comparison with both other agents (P < 0.01). The use of propofol was associated with increased risk of missed seizure (8.9%) compared with methohexital (3.9%) and thiopental (3.2%). Propofol was also associated with higher doses of administered energy, with a statistically significant difference (P = 0.018) observed between propofol and thiopental. Although propofol required the greatest energy delivery, it was associated with the shortest seizure durations. Methohexital resulted in the longest seizure duration, and thiopental was associated with the least amount of energy delivery with an intermediate seizure length.