title: Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: a molecular dynamics study.
abstract: Local anesthetics (LAs) are drugs that cause reversible loss of nociception during surgical procedures. Articaine is a commonly used LA in dentistry that has proven to be exceptionally effective in penetrating bone tissue and induce anesthesia on posterior teeth in maxilla and mandibula. In the present study, our aim was to gain a deeper understanding of the penetration of articaine through biological membranes by studying the interactions of articaine with a phospholipid membrane. Our approach involves Langmuir monolayer experiments combined with molecular dynamics simulations. Membrane permeability of LAs can be modulated by pH due to a titratable amine group with a pKa value close to physiological pH. A change in protonation state is thus known to act as a lipophilicity switch in LAs. Our study shows that articaine has an additional unique lipophilicity switch in its ability to form an intramolecular hydrogen bond. We suggest this intramolecular hydrogen bond as a novel and additional solvent-dependent mechanism for modulation of lipophilicity of articaine which may enhance its diffusion through membranes and connective tissue.
authors.affiliation: Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway. knut.teigen@biomed.uib.no
authors.forename: Age Aleksander
authors.initials: AA
authors.lastname: Skjevik
authors.forename: Bengt Erik
authors.initials: BE
authors.lastname: Haug
authors.forename: Henning
authors.initials: H
authors.lastname: Lygre
authors.forename: Knut
authors.initials: K
authors.lastname: Teigen
mesh_terms: D000779:Anesthetics, Local / Q000737:chemistry* / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000378:metabolism*; D002355:Carticaine / Q000737:chemistry* / Q000493:pharmacokinetics*; D004058:Diffusion; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000032:analysis
chemical_list: D000779:Anesthetics, Local; D010713:Phosphatidylcholines; D002355:Carticaine