Anesthetics GABAa receptor

The GABA-gated chloride ion channel is modulated by several classes of drugs that bind to allosteric sites on the receptor complex the benzodiazepines, barbiturates and related intravenous general anesthetics such as etomidate and propofol, as well as anesthetic steroids and endogenous neurosteroids. It appears that some types of GABAa receptor are directly enhanced by ethanol and volatile general anesthetics (Fig. 16-2) [7,8,20]. 

There are now indications for the interaction of progesterone metabolites with the Cl channel of the GABAa receptor (Fig. 52-7). The A-ring-reduced steroids, especially those with the 5a,3a configuration, are particularly active on the GABAa receptor [ 12]. By facilitating chloride-channel opening, these steroids produce anesthetic, anxiolytic and sedative-hypnotic effects (see Ch. 16). 

Rudolph U, Mohler FI Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol 2004 44 475. [PMID 14744255]... 

Jurd R et al General anesthetic actions in vivo strongly attenuated by a point mutation in the GABAa receptor beta3 subunit. FASEB J 2003 17 250. [PMID 12475885]... 

Nishikawa et al Volatile anesthetic actions on the GABAa receptors Contrasting effects of alpha 1(S270) and beta 2(N265) point mutations. Neuropharmacology 2002 42 337. [PMID 11897112]... 

Krasowski M D, Nishikawa K, Nikolaeva N et al 2001 Methionine 286 in transmembrane domain 3 of the GABAa receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics. Neuropharmacology 41 952-964 Kristinsson J, Thordarson T H, Johannesson T 1996 Pharmacokinetics of lignocaine in Icelandic horses after infiltration anaesthesia. Veterinary Record 138 111-112... 

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