Meyer-Overton rule

It thus follows that the membrane concentration of typical P-gp substrates for halfmaximum activation of P-gp falls in the range of 1 to 10 mmole drug per mole lipid. This is a much narrower concentration range than that required for the same substances in the aqueous phase 10 8 to 10 3 M. A similar phenomenon has been observed in anesthesia. The membrane concentration of anesthetics required for anesthesia has been found to be 33 mM, independent of the anesthetic applied (Meyer-Overton rule). 

E) Enantiomers of inhalational agents provide support for the Meyer Overton rule. 

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. 

Bovill J G 2000 Mechanisms of anaesthesia time to say farewell to the Meyer-Overton rule. Current Opinion in Anaesthesiology 13 433-436 Carter A J 1999 Dwale an anaesthetic from old England. British Medical Journal 319 1623-1626 (use of medicinal herbs to render a patient unconscious for surgery, before modem general anaesthesia)... 

Cantor, R. S. (2001). Breaking the Meyer-Overton rule Predicted effects of varying stiffness and interfecial activity on the intrinsic potency of anesthetics. Biophysical Journal, 80 ), 2284-2297. 

The Meyer-Overton hypothesis proposed that once a sufficient number of anaesthetic molecules were dissolved in the lipid membranes of cells within the central nervous system, anaesthesia would result by a mechanism of membrane disruption. While an interesting observation, there are several exceptions to the rule that make it insufficient to account fully for the mechanism of anaesthesia. 

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