Title: Articaine interaction with phospholipid bilayers
Author: Prates, érica Teixeira; Rodrigues Da Silva, Gustavo Henrique; Franco De Souza, Thais; Skaf, Munir S.; Pickholz, Mónica; De Paula, Eneida
Is part of: JOURNAL OF MOLECULAR STRUCTURE, v. 1222, p. 128854 -
Citation: Prates, érica Teixeira; Rodrigues Da Silva, Gustavo Henrique; Franco De Souza, Thais; Skaf, Munir S.; Pickholz, Mónica; De Paula, Eneida; Articaine interaction with phospholipid bilayers. JOURNAL OF MOLECULAR STRUCTURE, v.1222, p. 128854-, 2020
Abstract: Local anesthetics promote analgesia by interacting with excitable membranes. Articaine (ATC) has a unique composition among local anesthetics as it possesses a thiophene instead of the typical phenyl ring. Aiming to characterize the interaction of neutral articaine (nATC) with phospholipid membranes, we have employed a synergistic approach of experimental and computational techniques. Fluorescence measurements supported nATC partitioning into the membranes, since its intrinsic fluorescence anisotropy increased from 0.03 in water to 0.29 in the presence of egg phosphatidylcholine (EPC) liposomes, and the fluorescence of AHBA, a probe that monitors the water-membrane interface, was quenched by nATC. H-1 NMR experiments revealed changes in the chemical shifts of articaine and EPC hydrogens after partitioning, and shorter T-1 values of nATC hydrogens when inserted into the EPC vesicles. Contacts of nATC and the phospholipid polar head group were inferred from 2D-NOE. Taken together, these results indicate a superficial insertion of the nATC molecules inside EPC bilayers. This conclusion was confirmed by molecular dynamics simulations, which allowed the identification of the key interactions underlying the preferential location of nATC in the bilayer. Contrary to what is often stated (that articaine is a high lipophilic local anesthetic agent) our results place ATC among the hydrophilic ones, such as lidocaine, prilocaine, and mepivacaine, for which the water/membrane interface is the preferred location. (C) 2020 Elsevier B.V. All rights reserved.
Keywords: articaine; fluorescence; liposomes; local anesthetics; molecular dynamics; nuclear magnetic resonance;
Subjects: CIENCIAS_BIOLOGICAS; Biofísica de Processos e Sistemas;
Funding: The authors are grateful to Dr. Leonardo F. Fraceto (Sao Paulo State University, UNESP/Sorocaba, SP, Brazil) for the collection and treatment of NMR data and Dr. Amando S. Ito (FFCLRP/USP) for providing the AHBA fluorophore. We also thank FAPESP (#07/02629-2; #14/14457-5 grant; #17/15174-5), CNPq (#309625/2017-3), CONICET (#0131-2014), ANPCyT (#PICT-2014-3653) for finantial support and Aventis Pharma for kindly donate articaine.