Carborane-Derived Local Anesthetics are Isomer Dependent

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. Cage anesthetics: In a new local anesthetic, ortho‐boronicaine, the phenyl ring of lidocaine was replaced with a highly symmetric, ortho‐carborane cage. Hindlimb plantar injections in mice resulted in longer analgesic effects compared with lidocaine. ortho‐Boronicaine exhibited greater analgesic efficacy compared with lidocaine or the meta‐ and para‐carborane or adamantane derivatives.