SB705498 is an orally bioavailable, competitive antagonist of the capsaicin-mediated of TRPV1 receptors (pKis = 7.6; 7.5; and 7.3 for human, rat, and guinea pig, respectively). SB705498 rapidly and reversibly inhibits capsaicin-, acid-, or heat-mediated activation of human TRPV1[1].
SB705498 (0.3nM-1μM; preincubated for 30min) potently inhibits capsaicin-induced activation of human TRPV1 expressed in 1321N1 cells or HEK293 cells with apparent pKi of 7.5 or 7.6, respectively[1]. SB705498 (50nM; 30min) blocked the enhanced effect of Static magnetic field on cancer cell apoptosis[2].
SB705498 (10mg; injected into the ventricle; one time) did not affect the accumulation of water intake and can reduce [Ca2+] under normoxia conditions[3]. SB705498 (3-30mg/kg; po; 2h pre-treatment time) displays excellent activity at 10 and 30mg/kg po with good reversal of allodynia. SB705498 is also shown to give 80% reversal of allodynia in the guinea pig Freund's Complete Adjuvant model at 10mg/kg p.o[4].
References:
[1]Gunthorpe M J, Hannan S L, Smart D, et al. Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor[J]. Journal of Pharmacology and Experimental Therapeutics, 2007, 321(3): 1183-1192.
[2]Chen W T, Lin G B, Lin S H, et al. Static magnetic field enhances the anticancer efficacy of capsaicin on HepG2 cells via capsaicin receptor TRPV1[J]. PLoS One, 2018, 13(1): e0191078.
[3].Yang F, Zhou L, Wang D, et al. Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats[J]. Scientific Reports, 2016, 6(1): 30168.
[4]Khan A, Khan S, Kim Y S. Insight into pain modulation: nociceptors sensitization and therapeutic targets[J]. Current drug targets, 2019, 20(7): 775-788.
SB705498是一种口服生物可利用的、竞争性的辣椒素介导的TRPV1受体拮抗剂（人类、大鼠和豚鼠的pKis分别为7.6、7.5和7.3）。SB705498能够快速、可逆地抑制辣椒素、酸或热介导的人类TRPV1激活[1]。
SB705498（0.3nM-1μM；preincubated for 30min）可有效抑制辣椒素诱导的1321N1细胞或HEK293细胞中TRPV1蛋白激活，表观pKi分别为7.5或7.6[1]。SB705498（50nM；30min）可阻断静磁场对癌细胞凋亡的增强作用[2]。
SB705498（10mg；injected into the ventricle；one time） 不影响水分摄入的积累，并可在常氧条件下降低 [Ca2+][3]。SB705498(3-30mg/kg；po；2h pre-treatment time) 在10和30mg/kg口服剂量下表现出优异的活性，可很好地逆转异常性疼痛。SB705498在10mg/kg口服剂量下还显示出对豚鼠弗氏完全佐剂模型中异常性疼痛的80%逆转[4]。