Dear Readers:
Anesthesia
Many compounds will cause general anesthesia when inhaled. Among these are the familiar organic compounds such as ether and chloroform. To this can be added inorganic nitrous oxide (laughing gas), nitrogen (when encountered under pressure during diving) and the inert gas, xenon. These materials do not bear any similarity in chemical structure, and it lead one to the conclusion that anesthesia by these compounds is a physical phenomenon, especially when xenon is considered.
The Overton-Meyer hypothesis related anesthetic potency to the ratio of solubility of a compound in both water and oil (the lipid-water partition coefficient). It did not however state that this solubility was the cause of anesthesia , only that there was a correlation of some molecular property that was also related to anesthetic potency.
Mechanisms
Several decades ago, Mullins proposed that anesthetics would expand lipid cellular membranes and interfere, probably, with the transport of ions across them. [The movement of sodium and potassium ions is responsible for the conduction of the nerve signal.] The concept of expansion was based on the earlier observation that pressure applied to an anesthetized animal would reverse the anesthetic state. The hypothesis was that the conformation ( = shape) of the molecule/s of the membrane would change the diffusion ( rate of passage ) of ions through the lipid membrane. This passage, thus, would be made more difficult. The pressure can be applied by means of a piston or by a compressed gas that is itself non-narcotic. The only one that will work is helium.
The current speculation is that lipid membranes per se are not related to the ion exchange process. Proteins embedded within the membrane structure move the ions.
What Else?
Curiously, many biomacromolecules posses a three dimensional shape and these shapes are modified by pressure. Many animals will die if brought up to the surface from very deep depths. It is likewise thought that animals from the surface would eventually reach a point when pressure would begin to affect the structural integrity of the molecules. For example, raw eggs lowered to 10,000 feet in the ocean and brought up appear as if they were hard boiled. This is an example of denaturation and something similar would doubtlessly occur to a hapless diver making such an excursion.
Dr Deco :doctor:
References :book2:
Cullen S, Gross E. The anesthetic properties of xenon in animals and human beings, with additional observations on krypton. Science 1951; 113:580-582.
Franks N, Lieb W. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367:607-614.
Koblin D. Mechanisms of Action In: R. D. Miller, ed. Anesthesia. 5th ed. Philadelphia: Churchill Livingston, 2000; 48-73.
Mullins L. Some physical mechanisms in narcosis. Chem Rev 1954; 54:289-323.
Miller K, Paton W, Smith R, et al. The pressure reversal of general anesthesia and the critical volume hypothesis. Mol Pharmacol 1973; 9:131-143.
MR Powell. The Role of the Noble Gas Series in Molecular Pharmacology, In: A Guide to Molecular Pharmacology-Toxicology, Vol. II. Chapter 13. [R.M. Featherstone, ed.], Marcel Dekker, New York, (1973).
