A new look at the hemolytic effect of local anesthetics, considering their real membrane/water partitioning at pH 7.4

Biophysical Chemistry
S V MalheirosE de Paula

Abstract

The interaction of local anesthetics (LA) with biological and phospholipid bilayers was investigated regarding the contribution of their structure and physicochemical properties to membrane partition and to erythrocyte solubilization. We measured the partition into phospholipid vesicles-at pH 5.0 and 10.5-and the biphasic hemolytic effect on rat erythrocytes of: benzocaine, chloroprocaine, procaine, tetracaine, bupivacaine, mepivacaine, lidocaine, prilocaine, and dibucaine. At pH 7.4, the binding of uncharged and charged LA to the membranes was considered, since it results in an ionization constant (pK(app)) different from that observed for the anesthetic in the aqueous phase (pK(w)). Even though it occurred at a pH at which there is a predominance of the charged species, hemolysis was greatly influenced by the uncharged species, revealing that the disrupting effect of LA on these membranes is mainly a consequence of hydrophobic interactions. The correlation between the hemolytic activity and the LA potency shows that hemolytic experiments could be used for the prediction of activity in the development of new LA molecules.

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Citations

Nov 13, 2012·Expert Opinion on Drug Delivery·Eneida de PaulaFrancisco C Groppo
Nov 4, 2011·Journal of Drug Targeting·Roberta Aline Franco de LimaEneida de Paula
Aug 27, 2010·Expert Opinion on Drug Metabolism & Toxicology·Laurence E Mather
Sep 15, 2012·Biological & Pharmaceutical Bulletin·Anna JarominArkadiusz Kozubek
Mar 8, 2011·Chemistry and Physics of Lipids·K CyprychM Przybylo
Nov 18, 2008·Biophysical Chemistry·G S LoriteM A Cotta
Mar 18, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Chen SongWilly Nerdal
Nov 27, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Daniele R de AraujoEneida de Paula
Oct 5, 2010·British Journal of Pharmacology·Cf AlvesMh Napimoga
Dec 3, 2013·Chemical Biology & Drug Design·Lucas M ArantesSergio A Fernandes
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Jul 31, 2012·Biochimica Et Biophysica Acta·Nicole WeizenmannHolger A Scheidt
Aug 26, 2016·Journal of Molecular Modeling·Irene Wood, Mónica Pickholz
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Dec 10, 2019··Boyana PaarvanovaIvan T. Ivanov

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