Overton hypothesis

Pohorille, A. Wilson, M.A. New, M.H. Chipot, C., Concentrations of anesthetics across the water-membrane interface the Meyer-Overton hypothesis revisited, Toxicology Lett. 1998,100, 421 130. 

Meyer-Overton hypothesis, 17 376-377 Meyer-Schuster rearrangement,... 

The Meyer-Overton hypothesis is the theory of anaesthetic action which proposes that the potency of an anaesthetic agent is related to its lipid solubility. 

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. 

In 1954, Mullins, in a modification to the Overton hypothesis, proposed that besides the membrane concentration of the anesthetic, its volume, expressed as its volume fraction (mole fraction X partial molal volume), is important. This reasoning implied that the anesthetic, due to its solubility properties, expands the cell membrane, and that anesthesia occurs when a critical expansion value is reached, at about 0.3-0.5% of the original volume. 

BORONCOMPOUNDS - BORON OXIDES, BORIC ACID AND BORATES] (Vol 4) Meyer-Overton hypothesis... 

Ostwald solubility coefficient. The graph shows that an anaesthetic gas with a high oil solubility is effective at a low alveolar concentration and has a high potency. This relationship is the basis of the Meyer-Overton hypothesis of anaesthesia. 

The correlation between anaesthetic potency and lipid solubility shown in Fig. 2.10 is valid for most inhaled anaesthetics and the product MAC X oil/gas partition coefficient (which should of course be a constant) varies by only a factor of 2 or 3 for potencies ranging over 100 000-fold. This constancy implies that inhaled anaesthetics act in the same manner at a specific hydrophobic site (the so-called unitary theory of anaesthesia). This has been challenged by more recent work that has identified compounds, including alkanes and poly-halogenated and perfluorinated compounds, which do not obey the Meyer- Overton hypothesis. It has been suggested that a contributory cause of deviation from this hypothesis may be the choice of lipid to represent the anaesthetic site of action of these compounds, implying that there may be multiple sites of action for inhaled anaesthetics. 

J. Liu, M. J. Laster, S. Taheri, E. 1. et al. Effect of n-alkane kinetics in rats on potency estimations and the Meyer-Overton hypothesis. Anesth. Analg., 79, 1049-55 (1994)... 

In 1933, the Meyer-Overton hypothesis was examined relative to the hypnotic barbiturates by determining the distribution coefficients and other physical properties for a series of such derivatives (see Table 3.2, previous section) [146]. A parallelism between oil solubility and hypnotic... 

The second objective is to apply our knowledge of interfacial systems to a concrete problem of considerable medical interest - the determination of a relationship between the interfacial behavior of anesthetics and their anesthetic activity. This represents an alternative view to the century-old Meyer-Overton hypothesis [14,15], which relates anesthetic activity of anesthetics to their solubility in the bulk oily phase. 

According to the Meyer-Overton hypothesis [14,15], the anesthetic potency of anesthetic compounds is proportional to their solubilities in a non-polar phase, similar to the interior of the neuronal membrane. The remarkable aceuracy of this relationship for all elinical and many other anesthetics led to its broader interpretation that anes-theties act inside the neuronal membrane [36]. Then, the Meyer-Overton hypothesis implies that the same concentration is required for all anesthetics to exert anesthetic action, irrespective of their molecular structure. Their action may be either nonspecific or directed at selected membrane receptors. 

C. North andD.S. Cafiso. Contrasting membrane localization and behavior of halogenated cyclobutanes that follow or violate the meyer-overton hypothesis of general anesthetic potency. Biophys. J., 72 (1997) 1754-1761. 

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