Meyer-Overton theory, mechanism

There have been many attempts to produce a unified theory detailing the mechanism of action of inhalation anaesthetics but no single theory has been accepted. Early theories on the mechanism of action of inhalation anaesthetics can by summarised by means of the Meyer-Overton theory, which indicated that the potency of anaesthetic action was related to the lipophilicity of an anaesthetic compound. The Meyer-Overton theory suggested that lipids within the brain could be dissolved by anaesthetic agents, thereby interfering with brain cell activity, leading to anaesthesia. 

General anesthetics are soluble in lipids. Only a few are soluble in water. Furthermore, there is a well known correlation between anesthetic potency and lipid solubility. It is the Meyer-Overton rule that has been known for 80 years to researchers in anesthesia.. This relationship was thoroughly studied and reexamined in recent years (See ). In its most modem form the lipid solubility or oil/water partition coefTicient is plotted against the so-called righting reflex taken for a measure of anesthetic potency. It is log 1/p where p is the effective anesthetic pressure in atmospheres required to suppress the righting reflex of mice in half of the experimental animals On this relationship arc based the unitary hypothesis and the hydrophobic site theory which state that all general anesthetics act by the same mechanism at the same molecular or sub-cellular sites of the membrane and that the sites are hydrophobic. 

General anaesthetics have been in use for more than a centuiy, but unfortunately so far no exact mechanism of action has been put forward. Of coiuse, a few theories, namely lipid, physical, biochemical, miscellaneous, Meyer-Overton, minimum alveolar concentration (MAC), stereochemical effects and ion-channel and protein receptor theories have been advocated from time to time in support of the mode of action of the general anaesthetics. These will be discussed briefly in this context. 

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