Mode Of Action

General anaesthetics act on the brain, primarily on the midbrain reticular activating system. Many anaesthetics are lipid soluble and there is good correlation between this and anaesthetic effectiveness (the Overton-Meyer hypothesis); the more lipid soluble tend to be the more potent anaesthetics, but such a correlation is not invariable. Some anaesthetic agents are not lipid soluble and many lipid soluble substances are not anaesthetics. Until recently it was thought that the principal site of action of general anaesthetics was the neuronal lipid bilayer membrane. The current view is that their anaesthetic activity is caused by interaction with protein receptors. It is likely that there are several modes of action, but the central mechanism of action of volatile anaesthetics is thought to be facilitation at the inhibitory y-aminobutyric acid (GABAa) and glycine receptors. Agonists at these receptors open chloride ion channels and the influx of chloride ions into the neuron results in hyperpolarisation. This prevents propagation of nerve impulses and renders the patient unconscious. Some general anaesthetics increase the time that the chloride channels are open while others increase the frequency of chloride channel opening.

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