General Anesthetic Actions on GABAA Receptors

Abstract

General anesthetic drugs interact with many receptors in the nervous system, but only a handful of these interactions are critical for producing anesthesia. Over the last 20 years, neuropharmacologists have revealed that one of the most important target sites for general anesthetics is the GABAA receptor. In this review we will discuss what is known about anesthetic – GABAA receptor interactions.

Inhibition of learning and memory by general anesthetics

“…[123][124][125] Intravenous anesthetics, including etomidate, propofol, and barbiturates, enhance the GABA A receptor function, and this effect contributes to hypnosis, immobility, and memory blockade. 105,108,111,114,126,127 The halogenated volatile anesthetics (isoflurane, sevoflurane, and desflurane) also enhance GABA A receptor function, although these drugs appear to be less selective for GABA A receptors than most intravenous anesthetics. 105,128 Studies using site-directed mutagenesis suggest that GABA A receptors are not the sole mediators of volatile anesthetics.…”

General anesthetics in children: neurotoxic or neuroprotective?

“…[1,2] The recommended, until a few years ago was that general anesthesia would be a state of insensibility and chemically induced unconsciousness, propitiated for the performance of surgical or diagnostic procedures and at its end, people returned to their previous state, without any deficits from a physiological point of view [3][4][5][6].…”

Effect of clonidine on the target dose of propofol: bispectral index evaluation

“…Atropine was administered prophylactically with the first inhalant anaesthetic (chloroform) to attenuate chloroform's hypersialosis effect. [1] Although the mechanisms of action of general anaesthetics are still not completely understood, it is known that they act in various locations, with each medication acting in one specific location, [2] Currently, the most accepted theory is that anaesthetics act by stimulating [1] GABA A receptors, which inhibits NMDA receptors and blocks excitation at the cortical level. [2] Evidence suggests that some anaesthetic drugs have a neurotoxic effect that continues beyond the exposure time, altering genes and protein expression.…”

“…[1] Although the mechanisms of action of general anaesthetics are still not completely understood, it is known that they act in various locations, with each medication acting in one specific location, [2] Currently, the most accepted theory is that anaesthetics act by stimulating [1] GABA A receptors, which inhibits NMDA receptors and blocks excitation at the cortical level. [2] Evidence suggests that some anaesthetic drugs have a neurotoxic effect that continues beyond the exposure time, altering genes and protein expression. [3] Harmful effects have been recorded following exposure to ketamine, midazolam, propofol, isoflurane, sevoflurane, and desflurane.…”

“…The majority of hypnotics produce their effects by connecting to the inhibitory gamma-aminobutyric acid A (GABA A ) receptor, stimulating it or blocking the excitatory effect of the N-methyl-D-aspartate (NMDA) receptor. [2] Alpha-2 agonists, of which clonidine was the first to be approved for use in humans, act on the descending noradrenergic path to modulate pain, as well as on the 2 locus coeruleus, where they have a sedative effect. When used in association with general anaesthesia, clonidine permits the use of lower hypnotic doses, and some studies have shown an enhanced pain-modulating effect when it is administered in the intrathecal space.…”