ABT-639 is a T-type calcium channel blocker. It inhibits inactivated-state Cav3.2 channels with an IC50 value of 2.3 μM and inactivated-state Cav3.1 and Cav3.3 channels by 50 and 39%, respectively, when used at a concentration of 10 μM. ABT-639 selectively inhibits inactivated-state T-type calcium currents over resting-state currents in rat dorsal root ganglion (DRG) neurons (IC50s = 7.6 and >30 μM, respectively). It reverses the hind limb grip force deficit in a rat model of osteoarthritic pain induced by monoiodoacetic acid (MIA; ED50 = 2 mg/kg). ABT-639 also increases the paw withdrawal threshold in rat spinal nerve ligation (SNL) and chronic constriction injury (CCI) models of neuropathic pain in a dose-dependent manner and attenuates cold allodynia in the CCI rat model when administered at doses greater than or equal to 3 mg/kg.
ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain.ABT-639 produces robust antinociceptive activity in experimental pain models at doses that do not significantly alter psychomotor or hemodynamic function in the rat.
Zhang, Q., et al. "Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639."Acs Medicinal Chemistry Letters6.6(2015):150429091057009.
Serra, J, et al. "Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. " Pain 156.11(2015):2175.
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