SNX-482

SNX-482 is isolated from the venom of the spider Hysterocrates gigas.[1]

GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH[1]

SNX-482 is homologous to the spider peptides grammatoxin S1A and hanatoxin.[1]

Cav2.3 (alpha1E, R-type) channel (strong affinity), L-type Ca²⁺ channel, P/Q type Ca²⁺ channel, Na⁺ channel.[1][2][3] "SNX-482 [also] dramatically reduced the A-type potassium current in acutely dissociated dopamine neurons from mouse substantia nigra pars compacta." [4]

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][7]