The Influences of Side Chain Displacement of Local Anesthetics on Their Effects.

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In order to find the influences of side chain displacement of local anesthetics on their effects, methyl, ethyl and butyl ester derivatives of lidocaine were synthesized. The duration of action of butyl ester derivative was three times longer than lidocaine. It must be the results of small pKa (7.5) larger partition coefficient (1.13) and potent protein binding (89%).The interaction of lidocaine hydrochloride or lidocaine ester derivatives with lecithin vesicles was investigated by proton magnetic resonance (^1H-NMR) spectroscopy. Signal broadening of drug indicated the incorporation of the drug into the vesicle membrane. Positively charged nitrogen of lidocaine hydrochloride interacted with polar part of the lecithin vesicles. On the other hand, lidocaine ester derivatives indicated interaction with lecithin vesicles not only by positive charge of nitrogen but also by electrostatic effect of ester carbonyl group. This may be related with the prolonged duration of lidocaine ester derivatives.These results indicated the possibility that local anesthetics may bind with external lipid membrane and may occur the closure of sodium channel externally.