1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMilrinoneCat. No.: HY-14252CAS No.: 78415-72-2Synonyms: Win 47203分式: CHNO分量: 211.22作靶點: Phosphodiesterase (PDE)作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO :

2、50 mg/mL (236.72 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.75 mg/mL (13.02 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.75 mg/mL (13.02 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 MilrinonePDE3 抑制劑，也

3、 種強藥、管舒張藥。體外研究 Milrinone (1 M) increases PKA activity in hypoxic myocytes to normoxic levels. Milrinone (50 nM)normalizes TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptorphosphorylation 1. Milrinone significantly reduces NE-induced vasoconstriction, attenu

4、ating both NEsensitivity and maximal tension generation. Inhibition of ATP-sensitive K+ channels or voltage-gated K+channels do not prevent the milrinone-induced attenuation of NE responses 4.體內(nèi)研究 Milrinone (1 g/kg/min, i.v.) significantly reduces PAP, PVR (18.96 1.7%), and LAP (26.03 2.3%) inconges

5、tive heart failure (CHF) rats. Milrinone (1 mg/mL, inhalation) results in a near-maximal reduction ofPAP without significant effects on AP, decreases pulmonary artery pressure similarly in a larger collective ofCHF rats. Milrinone inhalation selectively increases cAMP but not cGMP plasma concentrati

6、ons in bothgroups. Repeated milrinone inhalations even reduce lung wet/dry weight ratio 2. Milrinone (49.5 g) largelyshifts the ESPVR upwards and significantly increases end-systolic pressure (ESP(0.08) and the systolicpressure-volume area (PVA(0.08) at a mid-range LV volume (0.08 mL/g myocardium).

7、Milrinone also slightlydecreases LV ESP(ESV) and decreased Ea 3.PROTOCOLAnimal In juvenile rats of 100 8 g body weight (bw), CHF is induced by supracoronary aortic banding. In brief, ratsAdministration 2 are anesthetized by intraperitoneal injection of ketamine (87 mg/kg bw) and xylazine (13 mg/kg b

8、w). Rats areplaced in the supine position, the chest wall is shaved, and a left thoracotomy is performed in the thirdintercostal space during ventilation with 100% O2. The ascending aorta is freed from connective tissue andpartially occluded by implantation of a titanium clip with a defined internal

9、 diameter of 0.8 mm. After surgicalclosure of the thorax, the rats are allowed to recover from anesthesia. For postoperative analgesia, ratsreceive 250 mg/kg bw of metamizole intramuscularly immediately after the operation and on the firstpostoperative day. Sham-operated rats serve as controls. Afte

10、r recovery from anesthesia, the animals areplaced in cages with free access to water and standard laboratory diet. For inhalation, milrinone (0.2-5mg/mL) or NaCl (0.9%) are nebulized using an ultrasonic nebulizer and inhaled for 3 min at identical peakinspiratory pressures as used throughout the exp

11、eriment. A 3-min nebulization of 1 mg/mL milrinone resultsin vaporization of 14 g of the phosphodiesterase-3 inhibitor as determined by microgravimetry. Therefore,the respective dose of 39 g/kg is analog to inhaled doses in human studies. For intravenous delivery,milrinone (initial bolus of 2-10 g/k

12、g, followed by 0.2-1 g/kg/min) or equivalent volumes of NaCl (0.9%; initialbolus of 1.6 mL/kg, followed by 10 L/kg/h) are administered by an infusion pump for 10 min.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Hum Mol Genet. 2019 Aug 6.

13、pii: ddz156. J Cell Physiol. 2019 Jan 11.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Santhosh KT, et al. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.Br J Pharm

14、acol. 2011 Jul;163(6):1223-36.2. Hentschel T, et al. Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model ofcongestive heart failure. Anesthesiology. 2007 Jan;106(1):124-31.3. Kishi T, et al. Effects of milrinone on left ventricular end-systolic pressure-volume relationship of rat hearts in situ. Clin Exp PharmacolPhysiol. 2001 Sep;28(9):737-42.4. Taylor MS, et al. Effect of milrinone on small mesenteric artery vasoconstriction: role of K(+) channels. Am J Physiol. 1999 J