Local anesthetics amphiphilic property

Most local anesthetics exist in part in the cationic amphiphilic form (cf. p. 208). This physicochemical property favors incorporation into membrane interphases, boundary regions between polar and apolar domains. These are found in phospholipid membranes and also in ion-channel proteins. Some evidence suggests that Na+-channel blockade results from binding of local anesthetics to the channel protein. It appears certain that the site of action is reached from the cytosol, implying that the drug must first penetrate the cell membrane (p. 206). 

As is well known, the bilayer structure of cell manbranes exhibits hydrophobic properties in the hydrocarbon part. This means that those molecules that must interact with the membrane interior must be hydrophobic. Anesthesia is brought about by the interaction between some suitable molecule and the lipid molecules in the biological membrane at the cell interface. The effect of pressure has been reported to be due to the volume change of membranes, which reverses the anesthesia effect. Local anesthetics are basically amphiphile molecules of tertiary amines, and some have colloidal properties in aqueous solution. The anesthetic power is determined by the hydrophobic part of the molecule. Surface tension measurements showed a correlation with the anesthetic power for a variety of molecules dibucane < tetracainebupivacainemepivacaine < lidocaine < procaine (aU as HCl salts). ... 

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