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Carborane Derived Local Anesthetics Show Isomer‐Dependent Analgesia
Author(s) -
Kracke George,
VanGordon Monika,
Kabytaev Kuanysh,
Sevryugina Yulia,
Kueffer Peter,
Jalisatgi Satish,
Hawthorne M.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.929.10
Subject(s) - carborane , lidocaine , analgesic , local anesthetic , chemistry , pharmacology , anesthesia , stereochemistry , medicinal chemistry , medicine
Clinically there is a need for local anesthetics with a greater specificity of action 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‐, dimethyl meta‐ and para‐carborane clusters. The boronicaine derivatives were tested for their analgesic activity and compared to lidocaine using standard procedures in mice following a plantar injection. The compounds differed in their analgesic activity in the following order: ortho‐carborane = dimethyl meta‐carborane > para‐carborane > lidocaine > meta‐carborane derivative. Both ortho‐boronicaine and 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. Financial support to G.R.K. from the University of Missouri Intellectual Property Fast Track Funding Program is acknowledged.