Department of Pharmaceutical Chemistry, Zaporozhye State Medical University, Maiakovskyi Avenue 26, Zaporizhzhia, 69000, Ukraine; Scientific Association "Farmatron", Maiakovskyi Avenue 26, Zaporizhzhia, 69000, Ukraine.
Scientific Association "Farmatron", Maiakovskyi Avenue 26, Zaporizhzhia, 69000, Ukraine; Department of Pharmacology and Medical Recipe, Zaporozhye State Medical University, Maiakovskyi Avenue 26, Zaporizhzhia, 69000, Ukraine.
Eur J Pharmacol. 2019 Jun 15;853:336-344. doi: 10.1016/j.ejphar.2019.04.013. Epub 2019 Apr 10.
Despite the success which was achieved in the treatment of arterial hypertension, the problem remains actual. At the departments of pharmaceutical chemistry and pharmacology of the Zaporozhye State Medical Institute (Ukraine), our research team isolated the compound 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril) as derivative of 4-amino-1,2,4-triazole. The objectives of this investigation were the study of cardioprotective and antihypertensive activities of this new compound Hypertril and we used the Spontaneously hypertensive rats (SHR) as an experimental model. We discovered that Hypertril has a reliable dose-dependent antihypertensive effect in the dose range 5-20 mg/kg after 30-day administration and this antihypertensive effect of Hypetril competes or significantly exceeds Metoprolol (20 mg/kg). Our studies obtained evidence of a dose-dependent improvement of myocardial energy metabolism. Hypertril reduces the manifestations of secondary mitochondrial dysfunction due to arterial hypertension. Hypertril can prevent oxidative modification of the protein; also Hypertril reduces the insufficiency of mitochondrial pores. As a result, Hypertril increases the content of ATP in the myocardium of SHR, normalizes the activity of mitochondrial enzymes, decreases lactate production and increases pyruvate. Hypertril enhances the cardioprotective effects of NO and increases the resistance of the cardiomyocytes to ischemia. The use of Hypertril leads to a dose-dependent increase of the density of cardiomyocyte nuclei, significant increase RNA content in nuclei and the cytoplasm of cardiomyocytes, and an increase of the nuclear-cytoplasmic index. These changes indicate a decrease of myocardial hypertrophy.
尽管在治疗动脉高血压方面取得了成功，但这个问题仍然存在。在扎波罗热国立医科大学（乌克兰）的药物化学和药理学系，我们的研究团队分离出了 1-(β-苯乙基)-4-氨基-1,2,4-三唑𬭩溴化物（Hypertril）作为 4-氨基-1,2,4-三唑的衍生物。本研究的目的是研究这种新化合物 Hypertril 的心脏保护和降压活性，并使用自发性高血压大鼠（SHR）作为实验模型。我们发现，Hypertril 在 30 天给药后，在 5-20mg/kg 的剂量范围内具有可靠的剂量依赖性降压作用，并且这种 Hypetril 的降压作用与美托洛尔（20mg/kg）竞争或显著超过美托洛尔。我们的研究获得了心肌能量代谢剂量依赖性改善的证据。Hypertril 减轻了由于动脉高血压引起的继发性线粒体功能障碍的表现。Hypertril 可以防止蛋白质的氧化修饰；还可以减少线粒体孔的不足。结果，Hypertril 增加了 SHR 心肌中的 ATP 含量，使线粒体酶的活性正常化，减少了乳酸的产生并增加了丙酮酸。Hypertril 增强了 NO 的心脏保护作用，并提高了心肌细胞对缺血的抵抗力。使用 Hypertril 可导致心肌细胞核密度、心肌细胞核和细胞质中 RNA 含量以及核质指数的剂量依赖性增加。这些变化表明心肌肥大减少。
