Is drug-induced membrane stabilization a selective or a non-specific phenomenon?
In his review of 1958, Shanes described stabilizers as agents which decrease or reduce an increase in the ionic permeability of excitable membranes, thus preventing a change in membrane potential or excitability. A large variety of compounds, including anaesthetics, can produce this pharmacological activity. Lipid solubility of the active compounds appears to be the major requirement and since these compounds are structurally unrelated, earlier theories of mechanism emphasized a common physical (non-specific) mode of action. This implies that specific sites and/or receptors are not involved. The interaction with hydrophobic sites results in a perturbation measured as fluidization or expansion of membrane components such as lipids and/or proteins. The perturbation would induce, either directly or indirectly, conformation change of ionic channels producing a decrease of induced depolarization (stabilization). There is considerable evidence, however, which does not support a common, non-specific mechanism of action for all excitable membrane stabilizers. The hypothesis that drug-induced membrane stabilization is selective and dependent on molecular structure in addition to lipid solubility is evaluated. Studies using in vitro neuronal preparations will be discussed which clearly demonstrate that stabilizers can differentially alter properties and function of neuronal membranes.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical