Bupivacaine and mepivacaine on artificial lipid membranes. a comparison of physicochemical parameters
Schlieper, P.
Der Anaesthesist 36(8): 436-441
1987
ISSN/ISBN: 0003-2417 PMID: 3661955 Document Number: 302642
Mepivacaine and bupivacaine, frequently used local anesthetics, differ in a variety of clinical effects but show only small differences in chemical structure. In order to learn more about molecular mechanisms of action, we investigated the effects of these two local anesthetics on artificial membranes and liposomes. Methods. Artificial membranes were formed from dipalmitoylphosphatidylcholine - cholesterol or from a phospholipid mixture extracted from rabbit heart to separate into two aqueous phases (100 mM NaCl, 1 mM glycine, pH 7.4). Membrane current and potential were recorded after addition of local anesthetics on one side of the membrane. Electrophoretic mobility of liposomes, formed from phosphatidylcholine and a mixture of phosphatidylcholine with phosphatidylinositol, was measured by laser Doppler techniques. The surface potential (zeta potential) was calculated by Gouy-Chapman theory. Lipid/buffer partition coefficients were determined in phosphatidylcholine liposomes by centrifugation and spectrophotometric measurement of the concentration. Results. Mepivacaine and bupivacaine induce concentration-dependent electrostatic potentials on artificial membranes, resulting from incorporation of the charged drug form. Bupivacaine is more active than mepivacaine. The time of onset is short for mepivacaine and delayed for bupivacaine. The effects are retarded in the presence of glucose and are higher and more rapid for the carbonized form of bupivacaine (CO2 form instead of hydrochloride form). The electrostatic surface potential, measured by electrophoretic liposome mobility, is changed by the local anesthetics.