General Depressant Drug Dependency: A Biophysical Hypothesis
We wish to propose a general hypothesis concerning the underlying physical effects and physiological changes that might lead to general-depressant drug dependency and to the manifestations of a general-depressant, withdrawal syndrome. To us it seems more important at this stage, and more in line with clinical observation, to accent the similarities between the wide range of C.N.S. depressants that are drugs of dependence, than to point to their differences. The hypothesis can be summarized as follows: Dependency occurs when the lipid composition of some critical membrane or membranes are modified so as to return the physical state (fluidity) of that membrane to its pre-affected value. The word ‘general’ is used here in the same sense as general depressant and general anaesthetic, it being now widely accepted that general anaesthesia is a non-specific effect induced by a wide range of chemically dissimilar compounds including even the noble gases, furthermore increased pressure antagonises anaesthesia (Miller, 1972) and increased temperature acts synergistically (Hill and Bangham, to be published). The recent proposed Gibbs free energy hypothesis of general anaesthesia (Hill, 1974) attempts to explain these effects at a fundamental thermodynamic level; thus the word ‘general’ implies a fundamental thermodynamic effect brought about by a wide range of different chemical compounds, which is neither fundamentally chemical nor biochemical, although the induced changes will result in biochemical modifications.
KeywordsGeneral Anaesthetic Withdrawal Syndrome Anaesthetic Concentration Biochemical Modification Membrane Concentration
Unable to display preview. Download preview PDF.
- Miller, K.W. Inert gas narcosis and animals under high pressure. In (Eds.) M.A. Sleigh and A.G. MacDonald) The Effects of Pressure on Organisms, Cambridge University Press, p. 363–378, 1972.Google Scholar
- Hill, M.W. The Gibbs free energy hypothesis of General Anaesthesia. In (Eds.) M.J. Halsey, J.A. Sutton and R.A. Miller. Molecular Mechanisms of General Anaesthesia. Churchill, Livingstone, p. 132–144, 1974 (in press)Google Scholar
- Jaffe, J.H. Drug addiction and abuse. In (Eds.) L.S. Goodman and A. Gilman) The Pharmacological Basis of Therapeutics 4th Edition, Macmillan, New York, 1970.Google Scholar
- Glasstone, S., Laidler, K.J. and Eyring, H. The Theory of Rate Processes. McGraw-Hill, New York. 1941.Google Scholar
- Melchior, D.L., Morowitz, H.J., Sturtevant, J.M. and Tsong, T.Y. Characterization of the plasma membrane of Mycoplasma laidlawii. Biochim. Biophys. Acta. Vol. 219, 114–122, 1970.Google Scholar
- Klein, R.A., Moore, M.J. and Smith, M.W. Selective diffusion of neutral amino acids across lipid bilayers. Biochim. Biophys. Acta. Vol. 233, 420–633, 1971.Google Scholar