Carborane-derived local anesthetics are isomer dependent.

George R Kracke, Monika R VanGordon, Yulia V Sevryugina, Peter J Kueffer, Kuanysh Kabytaev, Satish S Jalisatgi, M Frederick Hawthorne

Index: ChemMedChem 10(1) , 62-7, (2014)

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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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.