2-B-SS07-1 〇畠山 司¹、坪田 真帆¹、井場 祐里子¹、笠波 嘉人¹、関口 富美子¹、岡田 卓哉²、豊岡 尚樹²、川畑 篤史¹ Tsukasa Hatakeyama¹, Maho Tsubota¹, Yuriko Iba¹, Yoshihito Kasanami¹, Fumiko Sekiguchi¹, Takuya Takuya², Naoki Toyooka², Atsufumi Kawabata^{1 1}近畿大・薬・病態薬理、²富山大・工・生体機能性分子工学 ¹Lab. Pharmacol. Pathophysiol., Fac. Pharm., Kindai Univ., ²Fac. Engineer., Univ. Toyama H₂S generated by three different enzymes including cystathionine-β-synthase (CBS) contributes to somatic and visceral pain by enhancing the activity of Ca_v3.2, an isoform of T-type Ca²⁺ channels (T-channels). Most recently, we have developed KTtp38, a novel derivative of the antipsychotic pimozide, that potently inhibits T-channels, but has little affinity to D₂ receptors. Here, we investigated the effects of KTtp38 on Ca_v3.2-dependent pain, i.e. the somatic and/or colonic pain/hypersensitivity caused by Na₂S, an H₂S donor, or butyrate, and also on the colonic hypersensitivity caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Oral administration of KTtp38 potently suppressed somatic and visceral pain following intraplantar and intracolonic (i.col.) administration of Na₂S, respectively, and the colonic distention hypersensitivity following repeated i.col. butyrate. A single i.col. TNBS caused delayed colonic distention hypersensitivity accompanied by colonic CBS upregulation, which was inhibited by i.p. aminooxyacetic acid, a CBS inhibitor or deletion of Ca_v3.2 gene. Oral or i.p. KTtp38 suppressed the TNBS-induced colonic hypersensitivity. Thus, KTtp38 suppresses Ca_v3.2-dependent somatic and visceral pain, and is considered useful to treat pathological pain involving H₂S and/or Ca_v3.2.