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Sedative–hypnotics are a relatively new class of anesthetics, beginning with the introduction of sodium thiopental in the early 1930s. Since then, several ­sedative–hypnotics have been introduced (Table 6–1), with more in the drug development pipeline, such as remimazolam, fospropofol, and isomers of etomidate. Goals of these modified drugs include fast metabolism and breakdown as well as creating “soft” drugs with safer profiles. A major goal in developing methoxycarbonyl-etomidate is the removal of adrenocortical suppression by modifying the pyrrole ring in etomidate. Fospropofol is water-soluble as opposed to propofol, which is administered as an oil–water emulsion. In 2008, fospropofol was approved by the US Food and Drug Administration, although many clinical trials are still underway for specific uses of the drug.1

Table Graphic Jump Location
Table 6–1History of sedative–hypnotics.



Most sedative–hypnotics work via the γ-aminobutyric acid (GABA) receptor complex by enhancing the effect of GABA (Figure 6–1), the major inhibitory neurotransmitter in the central nervous system. GABA receptors are transmembrane, made up of 5 subunits (2 α, 2 β, 1 γ), with a central pore. There are several types of each subunit, leading to a variety of slightly different GABA receptors. Overall, there are 2 types: type A, a chloride channel, and type B, a potassium channel. Type ...

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