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• W2334131740 abstract "Abstract T-type Ca 2+ channels (T channels), particularly Ca v 3.2 among the 3 isoforms, play a role in neuropathic and visceral pain. We thus characterized the effects of RQ-00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human Ca v 3.1 or Ca v 3.2 by electrophysiological and fluorescent Ca 2+ signaling assays, and also evaluated the antiallodynic/antihyperalgesic activity of RQ in somatic, visceral, and neuropathic pain models in rodents. RQ-00311651 strongly suppressed T currents when tested at holding potentials of −65 ∼ −60 mV, but not −80 mV, in the Ca v 3.1- or Ca v 3.2-expressing cells. RQ-00311651 also inhibited high K + -induced Ca 2+ signaling in those cells. In mice, RQ, administered intraperitoneally (i.p.) at 5 to 20 mg/kg or orally at 20 to 40 mg/kg, significantly suppressed the somatic hyperalgesia and visceral pain-like nociceptive behavior/referred hyperalgesia caused by intraplantar and intracolonic administration of NaHS or Na 2 S, H 2 S donors, respectively, which involve the enhanced activity of Ca v 3.2 channels. RQ-00311651, given i.p. at 5 to 20 mg/kg, exhibited antiallodynic or antihyperalgesic activity in rats with spinal nerve injury–induced neuropathy or in rats and mice with paclitaxel-induced neuropathy. Oral and i.p. RQ at 10 to 20 mg/kg also suppressed the visceral nociceptive behavior and/or referred hyperalgesia accompanying cerulein-induced acute pancreatitis and cyclophosphamide-induced cystitis in mice. The analgesic and antihyperalgesic/antiallodynic doses of oral and i.p. RQ did not significantly affect the locomotor activity and motor coordination. Together, RQ is considered a state-dependent blocker of Ca v 3.1/Ca v 3.2 T channels and may serve as an orally available analgesic for treatment of neuropathic and inflammatory pain including distinct visceral pain with minimum central side effects." @default.
• W2334131740 created "2016-06-24" @default.
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• W2334131740 date "2016-03-23" @default.
• W2334131740 modified "2023-10-13" @default.
• W2334131740 title "Therapeutic potential of RQ-00311651, a novel T-type Ca2+ channel blocker, in distinct rodent models for neuropathic and visceral pain" @default.
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• W2334131740 doi "https://doi.org/10.1097/j.pain.0000000000000565" @default.
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