Urapidil Hydrochloride CAS 34661-75-1 URA

1. Peripheral effect
   Blocks postsynaptic adrenaline α1 receptors, inhibits the vasoconstrictive effect of catecholamines; rapidly expands peripheral blood vessels, reduces peripheral vascular resistance, and thus reduces cardiac afterload; at the same time, it can dilate venules, reduce venous blood return, and reduce cardiac preload. effect. It also has a moderate excitatory effect on presynaptic α2 receptors, thereby blocking the vasoconstriction and heart rate increase caused by the release of catecholamines, reducing cardiac afterload, increasing left ventricular output, maintaining a certain tension in blood vessels, and keeping blood pressure at a low level. As for unlimited lowering. Slight β1-receptor blockade inhibits the reactive heart rate increase caused by lowering of blood pressure and reduces myocardial oxygen consumption.

2. Central action
   It stimulates the central serotonin-1 receptor, blocks the sympathetic feedback of the medulla oblongata at the central level, reduces the activity of the sympathetic nervous system, plays a central hypotensive effect, and inhibits the reflex heart rate acceleration.
3. Promotes vasodilation
   Urapidil can stimulate tissue cells to release a large amount of calcitonin gene-related peptide (CGRP) into the blood circulation and increase the level of blood CGRP, thereby effectively antagonizing the effect of pulmonary endothelin (ET) on vasoconstriction, adjusting the imbalance of CGRP/ET ratio, promoting Dilation of blood vessels.
4. Other
   In addition, urapidil can effectively inhibit the release of ET in the lungs, reduce its activity, and inhibit its effect on weakening myocardial contractility.

Acute heart failure refers to a group of clinical syndromes caused by various reasons, such as sudden drop in cardiac output and sudden increase in cardiac preload and postload, among which acute left heart failure is the most common. In addition to the significant increase in circulatory resistance, insufficient tissue perfusion and other cardiovascular hemodynamic disorders, the upregulation of myocardial adrenergic α1 receptors, and the excessive secretion and release of catecholamines in acute heart failure lead to neuroendocrine disorders, which further induce arrhythmias and coronary artery contractions. , aggravating the vicious cycle of myocardial ischemia and hypoxia.

In addition to angiotensin-converting enzyme inhibitors and beta-blockers, urapidil is a potential new anti-heart failure drug that can rapidly relieve symptoms of heart failure, is safe and effective, and improves the prognosis of heart failure. The evidence is as follows:

1. Urapidil has a good anti-congestive heart failure effect;
2. Urapidil can well improve the cardiac function of ischemic heart failure;
3. Urapidil can inhibit and partially reverse ventricular remodeling and improve the compliance of the cardiovascular system;
4. Urapidil shows its own advantages when combined with insufficiency of major organs such as brain and kidney.

The application of urapidil in hypertensive crisis is relatively mature. In hypertensive crisis, urapidil has: ① Rapid onset of action, accurate and safe antihypertensive effect: blood pressure drops significantly after 5 minutes of medication, and reaches 20-30 minutes. Peak and remain stable; ② Organ protection effect: Urapidil can extensively expand the arteries and veins of pulmonary and systemic circulation, increase cardiac output, but not increase myocardial oxygen consumption, slightly increase blood flow of vital organs, and has target organ protection ③ The dose-effect relationship of urapidil is not strictly linear when the blood pressure is lowered, the blood pressure reduction effect does not increase with the increase of the dose, and the blood pressure is stable. ④ Small adverse reactions, except for nausea, dizziness and sweating caused by hypotension, no other adverse reactions have been found.

At present, the research on urapidil in blood pressure mainly focuses on the following aspects:

1. Preoperative and intraoperative application of urapidil in pheochromocytoma removal and other operations is helpful to counteract blood pressure fluctuations caused by catecholamines, and can better control intraoperative and postoperative blood pressure without obvious hypotension.
2. In pregnant women with pre-eclampsia and gestational hypertension, urapidil can dilate the umbilical-driven vein, does not significantly reduce the blood supply to the fetus, and has little effect on fetal accumulation, which can help pregnant women safely lower blood pressure during pregnancy.
3. Urapidil has a certain effect of lowering intraocular pressure. Although its mechanism is still under study, it can be safely used in glaucoma patients compared with nitrates.
4. There is no significant decrease in cerebral perfusion and no significant increase in intracranial pressure. Urapidil has advantages over calcium channel blockers and nitrates in the process of blood pressure lowering in cerebrovascular disease.

Urapidil can affect the ratio, differentiation and maturation of thymocytes CD4/CD8 cells, and its effect on humans remains to be further clarified. Experiments by Li et al. showed that urapidil has a certain effect on reducing hepatic venous wedge pressure and hepatic venous pressure gradient in liver cirrhosis. The specific mechanism of this effect remains to be further studied.