title: Carborane-derived local anesthetics are isomer dependent.
abstract: Clinically there is a need for local anesthetics with a greater specificity of action on target cells and longer duration. We have synthesized a series of local anesthetic derivatives we call boronicaines in which the aromatic phenyl ring of lidocaine was replaced with ortho-, meta-, C,C'-dimethyl meta- and para-carborane clusters. The boronicaine derivatives were tested for their analgesic activity and compared with lidocaine using standard procedures in mice following a plantar injection. The compounds differed in their analgesic activity in the following order: ortho-carborane = C,C'-dimethyl meta-carborane > para-carborane > lidocaine > meta-carborane derivative. Both ortho-boronicaine and C,C'-dimethyl meta-boronicaine had longer durations of analgesia than lidocaine. Differences in analgesic efficacies are rationalized by variations in chemical structure and protein binding characteristics.
authors.affiliation: Dept. of Anesthesiology & Perioperative Medicine, School of Medicine, University of Missouri, One Hospital Drive, Columbia, MO 65212 (USA); International Institute of Nano & Molecular Medicine, University of Missouri, 1514 Research Park Drive, Columbia, MO 65211-3450 (USA).
authors.forename: George R
authors.initials: GR
authors.lastname: Kracke
authors.forename: Monika R
authors.initials: MR
authors.lastname: VanGordon
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Sevryugina
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kueffer
authors.forename: Kuanysh
authors.initials: K
authors.lastname: Kabytaev
authors.forename: Satish S
authors.initials: SS
authors.lastname: Jalisatgi
authors.forename: M Frederick
authors.initials: MF
authors.lastname: Hawthorne
mesh_terms: D000779:Anesthetics, Local / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D019540:Area Under Curve; D001665:Binding Sites; D001880:Boranes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D002384:Catalysis; D020134:Catalytic Domain; D006801:Humans; D007536:Isomerism; D008012:Lidocaine / Q000737:chemistry; D051379:Mice; D062105:Molecular Docking Simulation; D010146:Pain / Q000188:drug therapy; D010165:Palladium / Q000737:chemistry; D012372:ROC Curve; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D001880:Boranes; D012709:Serum Albumin; D010165:Palladium; D008012:Lidocaine
keywords: carboranes; lidocaine; local anesthetic agents; pain; sensory blockade