364 RALPH S. LILLIE. 



narcosis the direct effect of the anaesthetic is limited to a surface- 

 action or adsorption affecting all of the colloids of the membrane; 

 in higher than the narcotizing concentrations the solvent action 

 of the anaesthetic upon the lipoids of the membrane assumes im- 

 portance and leads to disruptive and hence irreversible effects. 

 This view attributes the destructive action of anaesthetics in high 

 concentrations to a process different from that underlying true 

 anaesthesia. Meyer's experiments on the effects of temperature, 

 already cited, indicate, however, that solution of the anaesthetic 

 in the lipoids is an essential factor in the total physiological 

 effect. It is conceivable that a slight solution of this kind, com- 

 bined with the general increase in the viscosity of the proto- 

 plasmic surface-layer, may increase the stability of the mem- 

 brane; while a more pronounced solution may lead to direct 

 solvent or other structure-altering effects which destroy its semi- 

 permeability and so cause cytolysis. 



It must not be forgotten, however, that lipoid-solvents form 

 only one class of anaesthetics. Apparently all substances or 

 conditions which stabilize the membrane in a reversible manner 

 may exert anaesthetic action. Anaesthesia due to neutral salts, 

 cold, or the electric current, may be understood from this point 

 of view; salts or low temperature may stabilize the membrane 

 by causing gelation or other direct changes of aggregation in the 

 colloids; the electric current by altering its state of electrical 

 polarization. Some years ago I expressed this general view as 

 follows: "Anaesthetic action is due primarily to a modification 

 of the plasma-membrane of the cells or irritable elements, of such 

 a kind as to render these membranes more resistant towards 

 agencies which under the usual conditions rapidly increase their 

 permeability; cytolysis and stimulation, both of which depend 

 on such increase of permeability, are hence checked or prevented. 

 Decrease in the readiness with which the permeability is increased 

 thus involves for an irritable tissue decreased irritability; this 

 effect is produced by various salts, e. g., of magnesium, and by 

 ether and other lipoid-solvent anaesthetics in certain, not too 

 high, concentrations. ... It seems clear that for irritable tissues 

 the state of the lipoids in the plasma-membrane largely deter- 

 mines the readiness with which changes of permeability and 



