SNX-482

The compound was initially identified as a selective, voltage-dependent inhibitor of Cav2.3 (a1E, R-type) channels.^[1] SNX-482 inhibits native R-type Ca²⁺ currents at weak nanomolar concentrations in rat neurohypophyseal nerve terminals. However, it does not influence R-type Ca²⁺ currents at concentrations of 200–500 nM in several types of rat central neurons.^[1] Washout could only moderately reverse the R-type Ca²⁺ channel inhibition after treatment with 200 nM SNX-482. However, application of strong voltage reverses the blocking of R-type Ca²⁺ channels.^[2] SNX-482 needs to interact with a1E domains III and IV to play a role in the significant inhibition of R-type channel gating.^[2] Although SNX-482 is generally viewed as a selective inhibitor of Cav2.3 (a1E, R-type) channels, more recently it was shown that it can also inhibit L-type or P/Q type Ca²⁺ channels and incompletely block Na⁺ channels.^[1][2][3]

SNX-482 has been used to elucidate the roles of theaflavin-3-G in transmitter release.^[5] Furthermore, some research has indicated that it inhibits neuronal responses in a neuropathic pain model, so it is possible that SNX-482 can be used to reduce dorsal horn neuronal pain in neuropathic pain therapy.^[6]