title: R(+)-, Rac-, and S(-)-bupivacaine stereostructure-specifically interact with membrane lipids at cardiotoxically relevant concentrations.
abstract: It remains questionable whether local anesthetics can interact with membrane lipids at clinically relevant concentrations to show the difference between enantiomers. We compared the effects of bupivacaine stereoisomers on biomimetic membranes containing cardiolipin and cholesterol. Bupivacaine interacted with the membranes at cardiotoxic 5 μM with the potency being S(-)-enantiomer < racemate < R(+)-enantiomer, which agreed with the rank order of their cardiotoxicity. Such differences became greater with decreasing drug concentrations, possibly explaining the inconsistent cardiotoxic potencies of bupivacaine stereoisomers reported previously. The interactivity with biomembranes may in part contribute to the mode of toxic action of local anesthetics.
authors.affiliation: Department of Dental Basic Education, Asahi University School of Dentistry, Gifu, Japan. hiro@dent.asahi-u.ac.j
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Maki
authors.initials: M
authors.lastname: Mizogami
mesh_terms: D000779:Anesthetics, Local / Q000737:chemistry* / Q000633:toxicity*; D002045:Bupivacaine / Q000737:chemistry* / Q000633:toxicity*; D002308:Cardiolipins / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D007536:Isomerism; D008567:Membranes, Artificial; D013329:Structure-Activity Relationship
chemical_list: D000779:Anesthetics, Local; D002308:Cardiolipins; D008567:Membranes, Artificial; D002784:Cholesterol; D002045:Bupivacaine