CV-6209 (chloride) is a potent antagonist of the platelet-activating factor (PAF) receptor with the IC50 value of 75nM for rabbit platelets [1]. CV-6209 can attenuate the gastric mucosal injury induced by ischemia-reperfusion, and inhibit both an increase of thiobarbituric acid reactive substances and a decrease of α-tocopherol in gastric mucosa after ischemia-reperfusion [2]. CV-6209 has been widely used to inhibit the growth of Helicobacter pylori, as well as to suppress the bacterial motility and adhesion[3].
In vitro, CV-6209 treatment for 48h significantly inhibited the proliferation of U-343 MGa cells, with an IC50 value of 0.9μM[4]. Treatment of rat peritoneal macrophages with 10µM CV-6209 for 8 hours significantly inhibited the production of TNF-α induced by thapsigargin (46.1nM)[5].
In vivo, CV-6209 treatment via intraperitoneal injection at a dose of 0.2mg (dissolved in 0.2ml of physiological saline) every 8 hours for 6 days prevented pre-implantation thrombocytopenia in pregnant mice and reduced the number of implantation sites. [6]. One hour before aortic occlusion, a single intravenous dose of 1mg/kg of CV-6209 was administered, which effectively prevented cardiopulmonary ischemia-reperfusion injury in pigs[7]. A single intravenous injection of 1mg/kg dose of CV-6209 lasted for 1 minute, significantly alleviating the increase in portal venous pressure (PVP) caused by endotoxin in rats, and completely inhibiting hypotension[8].
References:
[1] Terashita Z I, Imura Y, Takatani M, et al. CV-6209, a highly potent antagonist of platelet activating factor in vitro and in vivo[J]. The Journal of pharmacology and experimental therapeutics, 1987, 242(1): 263-268.
[2] Yoshikawa T, Takahashi S, Naito Y, et al. Effects of a platelet-activating factor antagonist, CV-6209, on gastric mucosal lesions induced by ischemia-reperfusion[J]. Lipids, 1992, 27(12): 1058-1060.
[3] Iwao Y, Takano T, Taneike I, et al. Anti-Helicobacter pylori actions of CV-6209, a platelet-activating factor receptor antagonist[J]. The Journal of General and Applied Microbiology, 2013, 59(2): 147-152.
[4] Gati I, Bergström M, Muhr C, et al. Effects of the PAF-analog and-antagonist CV-6209 on cultured human glioma cell lines[J]. Prostaglandins, leukotrienes and essential fatty acids, 1991, 43(2): 103-110.
[5] Yamada M, Ichinowatari G, Tanimoto A, et al. Inhibition of tumor necrosis factor-α production by SK&F 98625, a CoA-independent transacylase inhibitor, in cultured rat peritoneal macrophages[J]. Life sciences, 1998, 62(20): PL297-PL302.
[6] Ando M, Suginami H, Matsuura S. Pregnancy Suppression by a Structurally Related Antagonist for Platelet Activating Factor, CV‐6209, in Mice[J]. Asia‐Oceania Journal of Obstetrics and Gynaecology, 1990, 16(3): 283-290.
[7] Qayumi K A, English J C, Feeley E J E, et al. A new platelet-activating factor antagonist (CV-6209) in preservation of heart and lung for transplantation[J]. Cardiovascular drugs and therapy, 1997, 11(6): 777-785.
[8] Kitagawa S, Kubota Y, Yamaguchi T, et al. Role of endogenous platelet‐activating factor (PAF) in endotoxin‐induced portal hypertension in rats[J]. Journal of gastroenterology and hepatology, 1992, 7(5): 481-485.
CV-6209 (chloride)是一种强效的血小板活化因子受体拮抗剂，对兔血小板的IC50值为75nM[1]。CV-6209可减轻缺血再灌注诱导的胃黏膜损伤，并抑制缺血再灌注后胃黏膜中thiobarbituric acid反应物质的增加和α-tocopherol的减少[2]。CV-6209已被广泛用于抑制幽门螺杆菌的生长以及抑制细菌的运动和粘附[3]。
在体外，CV-6209处理48小时显著抑制了U-343 MGa细胞的增殖，IC50值为0.9μM[4]。用10μM的CV-6209处理大鼠腹腔巨噬细胞8小时，显著抑制了thapsigargin (46.1nM)诱导的TNF-α的产生[6]。
在体内，每8小时腹腔注射0.2mg的CV-6209（溶于0.2ml生理盐水），连续6天，可预防孕鼠着床前血小板减少症并减少着床点数[6]。在主动脉阻断前1小时，单次静脉注射1mg/kg剂量的CV-6209，有效预防了猪的心肺缺血再灌注损伤[7]。单次静脉注射1mg/kg剂量的CV-6209持续1分钟，显著减轻了内毒素引起的大鼠门静脉压力升高，并完全抑制了低血压[8]。