The neuronal voltage-gated N-type calcium channel (Ca v2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived I?-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-I?-conotoxin GVIA displacement assay, a fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a whole-cell patch clamp electrophysiology assay with HEK293 cells stably expressing human Ca v2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of I?-conotoxin GVIA and found to be active in the 125I-I?- conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner.
Tranberg, C. E., Yang, A., Vetter, I., McArthur, J. R., Baell, J. B., Lewis, R. J., Tuck, K. L., & Duggan, P. (2012). Omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels. Marine Drugs, 10(10), 2349 - 2368. https://doi.org/10.3390/md10102349