P1075 is a potent activator of sulfonylurea receptor 2-related ATP-sensitive potassium channel (SUR2-KIR6) with an EC50 value of 45±10nM[1]. P1075 is a cyanoguanidine derivative that can increase anterior segment outflow capacity and reduce intraocular pressure[2]. P1075 can induce dilation of rat renal arteries[3]. P1075 can relax smooth muscle and shorten cardiac action potential duration (APD) in the nanomolar concentration range[4].
In vitro, P1075 (100μM) treatment of rabbit cardiomyocytes for 10min significantly induced the generation of intracellular ROS[5]. P1075 (30μM) treatment of rabbit ventricular myocytes significantly inhibited diazoxide-induced flavoprotein oxidation[6].
In vivo, P1075 (1μg/kg) treated by intravenous injection in rats with cardiac ischemia/reperfusion model significantly reduced the infarct size[7].
References:
[1] Schwanstecher M, Sieverding C, Dörschner H, et al. Potassium channel openers require ATP to bind to and act through sulfonylurea receptors[J]. The EMBO journal, 1998.
[2] Chowdhury U R, Bahler C K, Hann C R, et al. ATP-sensitive potassium (KATP) channel activation decreases intraocular pressure in the anterior chamber of the eye[J]. Investigative ophthalmology & visual science, 2011, 52(9): 6435-6442.
[3] Novakovic A, Pavlovic M, Milojevic P, et al. Different potassium channels are involved in relaxation of rat renal artery induced by P 1075[J]. Basic & clinical pharmacology & toxicology, 2012, 111(1): 24-30.
[4] Sargent C A, Sleph P G, Dzwonczyk S, et al. Cardioprotective effects of the cyanoguanidine potassium channel opener P-1075[J]. Journal of cardiovascular pharmacology, 1993, 22(4): 564-576.
[5] Oldenburg O, Yang X M, Krieg T, et al. P1075 opens mitochondrial KATP channels and generates reactive oxygen species resulting in cardioprotection of rabbit hearts[J]. Journal of molecular and cellular cardiology, 2003, 35(9): 1035-1042.
[6] Sato T, Nakaya H. P-1075 exerts diverse modulatory effects on mitochondrial ATP-sensitive K+ channels in rabbit ventricular myocytes[J]. Journal of cardiovascular pharmacology, 2006, 47(2): 165-168.
[7] Gross E R, Hsu A K, Gross G J. GSK3β inhibition and K ATP channel opening mediate acute opioid-induced cardioprotection at reperfusion[J]. Basic research in cardiology, 2007, 102: 341-349.
P1075是一种有效的、磺酰脲受体2相关的ATP敏感性的钾通道（SUR2-KIR6） 的激活剂，EC50值为45±10nM[1]。P1075是一种氰基胍衍生物，能够增加眼前节的流出能力，降低眼压[2]。P1075能够诱导大鼠肾动脉舒张[3]。P1075在纳摩尔浓度范围内可松弛平滑肌并缩短心肌动作电位持续时间（APD）[4]。
在体外，P1075（100μM）处理兔心肌细胞10min，显著诱导了细胞内ROS的生成[5]。P1075（30μM）处理兔心室肌细胞，显著抑制了二氮嗪诱导的黄素蛋白氧化[6]。
在体内，P1075（1μg/kg）通过静脉注射治疗心脏缺血/再灌注模型大鼠，显著减小了梗死面积[7]。