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. 1986 Jul;83(14):5116–5120. doi: 10.1073/pnas.83.14.5116

Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia.

N P Franks, W R Lieb
PMCID: PMC323901  PMID: 3460084

Abstract

Alcohols act as anesthetics only up to a certain chain length, beyond which their biological activity disappears. Although the molecular nature of general anesthetic target sites remains unknown, presently available data support the hypothesis that this "cutoff" in anesthetic activity could be due to a corresponding cutoff in the absorption of long-chain alcohols into lipid-bilayer portions of nerve membranes. To test this hypothesis, we have developed an extremely sensitive biological assay, based on inhibition of the light-emitting firefly luciferase reaction, which is capable of measuring lipid-bilayer/buffer partition coefficients K for very lipid soluble compounds. Contrary to the hypothesis and reported data, we find a strictly linear increase in log(K) as the chain length increases [delta(delta G0)CH2 = - 3.63 kJ/mol] for the primary alcohols from decanol to pentadecanol, with no hint of a cutoff. The fact that alcohols continue to partition into lipid bilayers long after their biological activity has ceased is consistent with the view that the primary target sites in general anesthesia are proteins rather than the lipid-bilayer portions of nerve membranes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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