Sarpogrelate hydrochloride is a highly selective 5-hydroxytryptamine (5-HT) 2 receptor antagonist (5-HT2A: pKi = 8.52; 5-HT2B: pKi = 6.57; 5-HT2C: pKi = 7.43) [1]. Sarpogrelate hydrochloride inhibits serotonin-induced platelet aggregation and promotes vasodilation, improving peripheral arterial blood flow [2]. Sarpogrelate hydrochloride is primarily used to treat peripheral arterial disease associated with intermittent claudication [3-4].
In human endothelial cells, Sarpogrelate (0.1-10μM; 24h) reverses the increase in monocyte adhesion to endothelial cells under high-glucose conditions [5]. In Raw 264.7 cells, Sarpogrelate hydrochloride (20μM; 24h) treatment inhibited LPS-stimulated macrophage migration and activation [6].
In tubulointerstitial injury mice model Sarpogrelate hydrochloride (3-300mg/kg; po; 4 weeks) can improve renal dysfunction and fibrosis pathological changes [7]. In endotoxin shock rat model, Sarpogrelate hydrochloride (0-30mg/kg; iv; single injection) treatment reduces the production of proinflammatory cytokines, alleviates lung damage, and reduces the mortality rate of endotoxic shock [8].
References:
[1]. Rashid M, Manivet P, Nishio H, et al. Identification of the binding sites and selectivity of sarpogrelate, a novel 5-HT2 antagonist, to human 5-HT2A, 5-HT2B and 5-HT2C receptor subtypes by molecular modeling[J]. Life sciences, 2003, 73(2): 193-207.
[2]. Miyazaki M, Higashi Y, Goto C, et al. Sarpogrelate hydrochloride, a selective 5-HT2A antagonist, improves vascular function in patients with peripheral arterial disease[J]. Journal of cardiovascular pharmacology, 2007, 49(4): 221-227.
[3]. Lu Y, Li J, Xie J, et al. Effects of sarpogrelate hydrochloride on peripheral arterial disease: A meta-analysis of randomized controlled trials[J]. Medicine, 2019, 98(46): e17266.
[4]. Ma B, Fan X, Liu P. Therapeutic effects of medication use on intermittent claudication: a network meta-analysis[J]. Journal of Cardiovascular Pharmacology, 2021, 77(2): 253-262.
[5]. Su Y, Mao N, Li M, et al. Sarpogrelate inhibits the expression of ICAM-1 and monocyte–endothelial adhesion induced by high glucose in human endothelial cells[J]. Molecular and cellular biochemistry, 2013, 373(1): 195-199.
[6]. Lee E S, Lee M Y, Kwon M H, et al. Sarpogrelate hydrochloride ameliorates diabetic nephropathy associated with inhibition of macrophage activity and inflammatory reaction in db/db mice[J]. PloS one, 2017, 12(6): e0179221.
[7]. Hamasaki Y, Doi K, Maeda-Mamiya R, et al. A 5-hydroxytryptamine receptor antagonist, sarpogrelate, reduces renal tubulointerstitial fibrosis by suppressing PAI-1[J]. American Journal of Physiology-Renal Physiology, 2013, 305(12): F1796-F1803.
[8]. Nishiyama T. Acute effects of sarpogrelate, a 5-HT2A receptor antagonist on cytokine production in endotoxin shock model of rats[J]. European journal of pharmacology, 2009, 614(1-3): 122-127.
Sarpogrelate hydrochloride是一种高选择性5-羟色胺（5-HT）2受体拮抗剂（5-HT2A: pKi = 8.52；5-HT2B: pKi = 6.57；5-HT2C: pKi = 7.43） [1]。Sarpogrelate hydrochloride可抑制血清素诱导的血小板聚集，促进血管扩张，从而改善外周动脉血流 [2]。盐酸沙格雷酯主要用于治疗间歇性跛行相关的外周动脉疾病 [3-4]。
在人内皮细胞中，Sarpogrelate hydrochloride（0.1-10μM; 24h）可逆转高糖条件下单核细胞粘附于内皮细胞的增加 [5]。在Raw 264.7细胞中，Sarpogrelate hydrochloride（20μM；24h）处理可抑制LPS刺激的巨噬细胞迁移和活化 [6]。
在肾小管间质损伤小鼠模型中，Sarpogrelate hydrochloride（3-300mg/kg；po；4周）可改善肾功能障碍和纤维化病理改变 [7]。在内毒素休克大鼠模型中，Sarpogrelate hydrochloride（0-30mg/kg；iv；单次注射）治疗可减少促炎细胞因子的产生，减轻肺损伤，降低内毒素休克的死亡率 [8]。