盐酸考尼伐坦作用机制 - Medchemexpress - MCE中国

1、Product Data SheetConivaptan hydrochlorideCat. No.: HY-18347ACAS No.: 168626-94-6分式: CHClNO分量: 535.04作靶点: Vasopressin Receptor作通路: GPCR/G Protein储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性数据体外实验 DMSO : 100 mg/mL (186.90 mM)* means soluble, but satu

2、ration unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.8690 mL 9.3451 mL 18.6902 mL5 mM 0.3738 mL 1.8690 mL 3.7380 mL10 mM 0.1869 mL 0.9345 mL 1.8690 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month (protect from light)。-80C 储存时，请在 6 个内使，-20

3、C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.67 mM); Clear solution此案可获得

4、2.5 mg/mL (4.67 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.67 mM); Clear solution此案可获得 2.5 mg/mL (4.67 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 2

5、5.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合Page 1 of 2 www.MedChemE均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.67 mM); Clear solution此案可获得 2.5 mg/mL (4.67 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 C

6、onivaptan hydrochloride种肽段类的 vasopressin receptor 拮抗剂，能够抑制肝脏的 V1A 受体 和 肾脏的V2 受体，Ki 值分别为 0.48 和 3.04 nM。IC & Target Ki: 0.48 nM (V1A receptor), 3.04 nM (V2 receptor)体内研究 Conivaptan (0.03, 0.1 and 0.3 mg/kg, i.v.) dose-dependently increases urine volume and reduces urine osmolality inboth myocardial i

7、nfarction and sham-operated rats. Conivaptan (0.3 mg/kg i.v.) significantly reduces right ventricularsystolic pressure, left ventricular end-diastolic pressure, lung/body weight and right atrial pressure in myocardialinfarction rats. Conivaptan (0.3 mg/kg i.v.) significantly increases dP/dt(max)/lef

8、t ventricular pressure in myocardialinfarction rats1. Conivaptan produces an acute increase in urine volume (UV), a reduction in osmolality (UOsm) and,at the end of the investigation, cirrhotic rats receiving the V(1a)/V(2)-AVP receptor antagonist does not showhyponatremia or hypoosmolality. Conivap

9、tan also normalizes U(Na)V without affecting creatinine clearance andarterial pressure2. Conivaptan (0.01 to 0.1 mg/kg, i.v.) exerts a dose-dependent diuretic effect in dogs without anincrease in the urinary excretion of electrolytes, inhibits the pressor effect of exogenous vasopressin in a dose-de

10、pendent manner (0.003 to 0.1 mg/kg i.v.) and, at the highest dose (0.1 mg/kg i.v.), almost completely blocksvasoconstriction caused by exogenous vasopressin. Conivaptan (0.1 mg/kg, i.v.) improves cardiac function, asevidenced by significant increases in left ventricular dP/dtmax, cardiac output and

11、stroke volume, and reducespreload and afterload, as evidenced by significant decreases in left ventricular end-diastolic pressure and totalperipheral vascular resistance in dogs with congestive heart failure3.PROTOCOLAnimal At 4 weeks after the operation, 39 myocardial infarction rats survived. Thir

12、ty are randomly selected without bias andAdministration 1 divided into five groups such that the distribution of infarct size and body weight among groups are similar, andgiven vehicle, conivaptan (0.03, 0.1 and 0.3 mg/kg) or SR121463A (0.3 mg/kg) by intravenous administration. Shamrats are also div

13、ided into four groups and given vehicle or conivaptan (0.03, 0.1 and 0.3 mg/kg) by intravenousadministration. Rats are then placed individually in metabolic cages and urine is collected for 3 h. Urine osmolality ismeasured by the freezing point depression method using an osmometer.MCE has not indepe

14、ndently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Front Pharmacol. 2019; 10: 1380. Neurogastroenterol Motil. 2019 Feb;31(2):e13493. Eur J Pharmacol. 2020 Apr 29:173157. Biomed J. 2020 May 23.Page 2 of 3 www.MedChemESee more customer validations on HYPERLINK www

15、.MedChemE www.MedChemEREFERENCES1. Wada K, et al. Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-inducedcongestive heart failure. Eur J Pharmacol. 2005 Jan 10;507(1-3):145-51. Epub 2005 Jan 1.2. Fernandez-Varo G, et al. Effect

16、of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats withcirrhosis and ascites. J Hepatol. 2003 Jun;38(6):755-61.3. Yatsu T, et al. Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure. Eur J Pharmacol. 19