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ABT-639

CAS No. : 1235560-28-7

MCE 国际站：ABT-639

产品活性：ABT-639 是一种新型选择性的 T 型 Ca²⁺ 通道阻滞剂。

研究领域：Membrane Transporter/Ion Channel  |  Neuronal Signaling

作用靶点：Calcium Channel

In Vivo: ABT-639 blocks recombinant human T-type (Ca_v3.2) Ca²⁺ channels in a voltage-dependent fashion (IC₅₀=2 μM) and attenuates low voltage-activated (LVA) currents in rat DRG neurons (IC₅₀=8 μM). ABT-639 is significantly less active at other Ca²⁺ channels (e.g. Ca_v1.2 and Ca_v2.2) (IC₅₀>30 mM). ABT-639 has high oral bioavailability (%F=73), low protein binding (88.9%) and a low brain:plasma ratio (0.05:1) in rodents. Following oral administration ABT-639 produces dose-dependent antinociception in a rat model of knee joint pain (ED₅₀=2 mg/kg, p.o.). ABT-639 (10-100 mg/kg, p.o.) also increases tactile allodynia thresholds in multiple models of neuropathic pain (e.g. spinal nerve ligation, CCI, and vincristine-induced, and capsaicin secondary hypersensitivity). ABT-639 does not attenuate hyperalgesia in inflammatory pain models induced by complete Freund’s adjuvant or carrageenan. At higher doses (e.g. 100-300 mg/kg) ABT-639 does not significantly alter hemodynamic or psychomotor function. The antinociceptive profile of ABT-639 provides novel insights into the role of peripheral T-type (Ca_v3.2) channels in chronic pain states.

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