Picotamide is a platelet aggregation inhibitor with an IC50 value of 0.76μM[1]. Picotamide can inhibit the thromboxane A2 (TxA2) receptor and TxA2 synthase, prevent platelet aggregation, and regulate the inflammatory process of atherosclerotic plaques[2]. Picotamide has been widely used as a model compound to develop a series of derivatives for inhibiting platelet aggregation[3].
In vitro, Picotamide treatment at 300μM for 45 minutes inhibited the contraction of hyperplastic human prostate smooth muscle induced by adrenergic and thromboxane[4]. Treatment with 300μM Picotamide for 45 minutes inhibited in the smooth muscle contractions induced by the phenylephrine, U46619, and electric field stimulation (EFS) in the lower urinary tract tissues[5]. Treatment with 300μM Picotamide for 30 minutes inhibited the smooth muscle contraction of the interlobular arteries in porcine renal interloba induced by phenylephrine [6].
In vivo, Picotamide treatment via intraperitoneal injection at a single dose of 375mg/kg 1 hour before thrombotic challenge could protect mice from death caused by intravenous injection of collagen plus epinephrine, and reduced the decline in circulating platelet count and pulmonary thromboembolism[7].
References:
[1] Liu X J, Shi X X, Zhong Y L, et al. Design, synthesis and in vitro activities on anti-platelet aggregation of 4-methoxybenzene-1, 3-isophthalamides[J]. Bioorganic & medicinal chemistry letters, 2012, 22(21): 6591-6595.
[2] Celestini A, Violi F. A review of picotamide in the reduction of cardiovascular events in diabetic patients[J]. Vascular Health and Risk Management, 2007, 3(1): 93-98.
[3] Zou J, Gao P, Hao X, et al. Recent progress in the structural modification and pharmacological activities of ligustrazine derivatives[J]. European Journal of Medicinal Chemistry, 2018, 147: 150-162.
[4] Hennenberg M, Miljak M, Herrmann D, et al. The receptor antagonist picotamide inhibits adrenergic and thromboxane-induced contraction of hyperplastic human prostate smooth muscle[J]. American Journal of Physiology-Renal Physiology, 2013, 305(10): F1383-F1390.
[5] Hennenberg M, Tamalunas A, Wang Y, et al. Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region[J]. European journal of pharmacology, 2017, 803: 39-47.
[6] Li B, Huang R, Wang R, et al. Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries[J]. Pharmacology Research & Perspectives, 2021, 9(3): e00771.
[7] Gresele P, Corona C, Alberti P, et al. Picotamide protects mice from death in a pulmonary embolism model by a mechanism independent from thromboxane suppression[J]. Thrombosis and haemostasis, 1990, 64(05): 080-086.
Picotamide是一种血小板聚集抑制剂，IC50值为0.76µM[1]。Picotamide可抑制血栓素A2（TxA2）受体和TxA2合酶，防止血小板聚集，并调节动脉粥样硬化斑块的炎症过程[2]。Picotamide已被广泛用作模型化合物，以开发一系列用于抑制血小板聚集的衍生物 [3]。
在体外，使用300µM的Picotamide处理45分钟，抑制了肾上腺素能和血栓素诱导的增生性人前列腺平滑肌收缩[4]。使用300µM的Picotamide处理45分钟，抑制了下尿路组织中由phenylephrine、U46619和电场刺激（EFS）诱导的平滑肌收缩[5]。使用300µM的Picotamide处理30分钟，抑制了phenylephrine诱导的猪肾叶间动脉的平滑肌收缩[6]。
在体内，血栓形成激发前1小时单次腹腔注射Picotamide（375mg/kg），可保护小鼠免于因静脉注射胶原蛋白加肾上腺素引起的死亡，并减轻了循环血小板计数的下降和肺血栓栓塞[7]。