SB 204741 is a selective and high affinity 5-HT2B antagonist with a pKi value of 7.1[1]. 5-HT2B receptor is a serotonin receptor subtype closely associated with cardiovascular remodeling, fibrosis, and inflammatory responses[2]. SB 204741 is commonly used in the research of cardiovascular diseases[3].
In vitro, SB 204741 (30µM; 30min) completely blocked the potentiating effect of a-Me-5-HT on N-methyl-D-aspartate(NMDA)-induced depolarizations, and inhibited the G-protein-coupled 5-HT2B-NMDA cross-signaling in frog motoneurones[4]. Treatment of TGF-β1-stimulated human peritoneal fibroblasts (HPFBs) with SB 204741 (1µM; 24h) significantly reduced the expression of profibrotic genes(COL1A1, COL1A2, ACTA2, CTGF, FN1, and TGF-B1) and pro-inflammatory cytokines(IFN-γ, IL-4, IL-17, IL-1β, IL-6, TNF-α), and increased anti-inflammatory cytokine IL-10 levels[5].
In vivo, SB 204741 (0.5mg/kg; i.p.; single administration) significantly decreased the percentage maximal possible effect (%MPE) in both tail-flick (TF) and hot-plate (HP) assays in rats exposed to 5mT electromagnetic field (EMF), and reduced analgesic activity in the EMF-induced analgesia model[6]. SB 204741 (1mg/kg/day; i.p.; 28 days) significantly reduced heart weight/body weight ratio, left ventricular weight/body weight ratio, myocyte area and interstitial fibrosis, improved mean arterial pressure, left ventricular end diastolic pressure, rate of contraction and rate of relaxation, and decreased hypertrophic, inflammatory and apoptotic markers while increasing Bcl-2 expression and phosphorylation of Akt/GSK-3β/β-catenin/eNOS in isoproterenol-induced cardiac hypertrophy in rats[7].
References:
[1] Bonhaus DW, Bach C, DeSouza A, et al. The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol. 1995;115(4):622-628.
[2] McCorvy JD, Roth BL. Structure and function of serotonin G protein-coupled receptors. Pharmacol Ther. 2015;150:129-142.
[3] Bai CF, Liu JC, Zhao R, et al. Role of 5-HT 2B receptors in cardiomyocyte apoptosis in noradrenaline-induced cardiomyopathy in rats. Clin Exp Pharmacol Physiol. 2010;37(7):e145-e151.
[4] Holohean AM, Hackman JC. Mechanisms intrinsic to 5-HT2B receptor-induced potentiation of NMDA receptor responses in frog motoneurones. Br J Pharmacol. 2004;143(3):351-360.
[5] Chaturvedi S, Singh H, Agarwal V, Jaiswal A, Prasad N. Unravelling the role of Sildenafil and SB204741 in suppressing fibrotic potential of peritoneal fibroblasts obtained from PD patients. Front Pharmacol. 2024;14:1279330.
[6] Ozdemir E, Demirkazik A, Taskıran AS, Arslan G. Effects of 5-HT1 and 5-HT 2 Receptor Agonists on Electromagnetic Field-Induced Analgesia in Rats. Bioelectromagnetics. 2019;40(5):319-330.
[7] Bharti S, Singh R, Chauhan SS, Hussain T, Al-Attas OS, Arya DS. Phosphorylation of Akt/GSK-3β/eNOS amplifies 5-HT2B receptor blockade mediated anti-hypertrophic effect in rats. FEBS Lett. 2012;586(2):180-185.
SB 204741是一种选择性且高亲和力的5-HT2B受体拮抗剂，其pKi值为7.1[1]。5-HT2B受体是一种与心血管重塑、纤维化及炎症反应密切相关的血清素受体亚型[2]。SB 204741常用于心血管疾病的研究[3]。
在体外实验中，SB 204741（30µM；30分钟）完全阻断了a-Me-5-HT对N-甲基-D-天门冬氨酸（NMDA）诱导的蛙运动神经元去极化的增强作用，并抑制了蛙运动神经元中G蛋白偶联的5-HT2B-NMDA交叉信号[4]。在TGF-β1刺激的人腹膜成纤维细胞（HPFBs）中，SB 204741（1µM；24小时）显著降低了促纤维化基因（COL1A1、COL1A2、ACTA2、CTGF、FN1 和 TGF-B1）和促炎细胞因子（IFN-γ、IL-4、IL-17、IL-1β、IL-6、TNF-α）的表达，并增加了抗炎细胞因子IL-10的水平[5]。
在体内实验中，SB 204741（0.5mg/kg；腹腔注射；单次给药）显著降低了在5mT电磁场（EMF）暴露的大鼠在甩尾（TF）和热板（HP）试验中的最大可能效应百分比（%MPE），减少了EMF诱导的镇痛模型中的镇痛活性[6]。SB 204741（1mg/kg/天；腹腔注射；28天）显著降低了异丙肾上腺素诱导的心脏肥大大鼠的心重/体重比、左心室重/体重比、心肌细胞面积和间质纤维化，改善了平均动脉压、左心室舒张末期压、收缩率和舒张率，并降低了肥大、炎症和凋亡标志物，同时增加了Bcl-2表达和Akt/GSK-3β/β-catenin/eNOS的磷酸化[7]。