Revizinone (R80122)
(Synonyms: 瑞维齐农,R80122) 目录号 : GC32495
Revizinone (R80122) 是一种新型选择性磷酸二酯酶 (PDE) 抑制剂，该酶的 IC50 值为 0.036 microM。
Cas No.:133718-29-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Revizinone is a novel selective phosphodiesterase (PDE) inhibitor with IC50 values on this enzyme to 0.036 microM. target: phosphodiesterase (PDE)[3]; IC 50: 0.036 microM; [3]In vivo: The administration of Revizinone improved the haemodynamic profile with an increase in cardiac output, a decrease in systemic vascular resistance and a stable heart rate and mean arterial blood pressure. [1] With regard to reconstitution of contractility and cardiac function Revizinone (E-isomer) was 10 fold more potent than R 79595 and nearly 100 fold more potent than R 80123 (Z-isomer). [2] Revizinone significantly increased global LV function and systolic wall thickening in ischemic areas at doses greater than or equal to 0.16 mg/kg i.v. [4]
[1]. Herregods L et al. Haemodynamic effects of R 80122 immediately after cardiopulmonary bypass; preliminary results. Anaesthesia. 1994 Aug;49(8):719-22. [2]. Schneider J et al. Cardiac effects of R 79595 and its isomers (R 80122 and R 80123) in an acute heart failure model. A new class of cardiotonic agents with highly selective phosphodiesterase III inhibitory properties. Naunyn Schmiedebergs Arch Pharmacol. 1992 Nov;346(5):563-72. [3]. de Cheffoy de Courcelles D et al. Inhibition of human cardiac cyclic AMP-phosphodiesterases by R 80122, a new selective cyclic AMP-phosphodiesterase III inhibitor: a comparison with other cardiotonic compounds. J Pharmacol Exp Ther. 1992 Oct;263(1):6-14. [4]. Vandeplassche GM et al. Comparative effects of R 80122, enoximone, and milrinone on left ventricular phosphodiesterase isoenzymes in vitro and on contractility of normal and stunned myocardium in vivo in dogs. J Cardiovasc Pharmacol. 1992 May;19(5):714-22.
| Cas No. | 133718-29-3 | SDF | |
| 别名 | 瑞维齐农,R80122 | ||
| Canonical SMILES | O=C(N(C1CCCCC1)C)CO/N=C(C2=CC=CC=C2)/C3=CC4=C(N=C(NC(C5)=O)N5C4)C=C3.[(E)] | ||
| 分子式 | C26H29N5O3 | 分子量 | 459.54 |
| 溶解度 | DMSO : ≥ 4.6 mg/mL (10.01 mM) | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1761 mL | 10.8804 mL | 21.7609 mL |
| 5 mM | 0.4352 mL | 2.1761 mL | 4.3522 mL |
| 10 mM | 0.2176 mL | 1.088 mL | 2.1761 mL |
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动物平均体重 | g | |
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Effects of the new phosphodiesterase-III inhibitor R80122 on contractility and calcium current in human cardiac tissue
J Cardiovasc Pharmacol 1994 Jul;24(1):133-43.PMID:7521478DOI:10.1097/00005344-199407000-00021.
The selective phosphodiesterase III (PDE-III) inhibitor R80122 ((E)-N-cyclohexal-N-methyl-2-[[[phenyl-(1,2,3,5- tetrahydro-2-oxoimidazo-[2,1b]-quinazolin-7-yl)-methylene]-a mino]-oxy]-acetamide) has been reported to possess greater cardiotonic potency and less side effects than the standard compounds milrinone or enoximone. To characterize this new compound further, we investigated the effects of R80122 on force of contraction (Fc) and calcium current (ICa) in human right atrium (HRA) and human left ventricle (HLV) with reference to the nonselective PDE-inhibitor IBMX (3-isobutyl-1-methylxanthine). With "late" exposure (300- to 330-min equilibration) of human atrial trabeculae, R80122 (3 microM) increased Fc by 60 +/- 11%; log EC50 was -6.2 +/- 0.1. R80122 (3 microM) induced a relative leftward shift of forskolin concentration-response curves by 0.34 log units; the respective value for IBMX (20 microM) was 0.46. A positive inotropic effect of R80122 was also shown in guinea pig papillary muscles. ICa was measured in voltage-clamped isolated myocytes of human right atrial and left ventricular (LV) tissue, and, for comparison, guinea pig ventricle. With clamp steps from -40 to +5 mV, R80122 (3 microM) increased peak ICa from 3.1 +/- 0.2 to 5.4 +/- 0.3 pA/pF in HRA cells, from 2.9 +/- 0.4 to 5.1 +/- 0.6 pA/pF in HLV cells, and from 4.4 +/- 0.3 to 6.6 +/- 0.5 pA/pF in guinea pig myocytes. IBMX 20 microM increased ICa to a greater extent. Washout or addition of carbachol 10 microM partially reversed the effect of R80122. Voltage dependence, inactivation time course, and steady-state inactivation of ICa were little changed by either compound. Stimulation of Ca2+ influx by L-type Ca2+ channels contributes to the positive inotropic effect of the selective PDE-III inhibitor R80122.
Cardiac and hemodynamic effects of intravenous R80122, a new phosphodiesterase III inhibitor, in a canine model of myocardial ischemia and heart failure
J Cardiovasc Pharmacol 1992 Jul;20(1):18-24.PMID:1383627doi
The cardiac and hemodynamic effects of R80122, a new specific phosphodiesterase III inhibitor, were studied in a closed-chest canine model of acute global left ventricular ischemia complicated by heart failure. The results obtained were compared with those obtained with milrinone. Intravenous infusion of the compounds (0.005 mg/kg/min for both) was started when stable heart failure had developed and was continued for 50 min followed by a washout period of 60 min. Both R80122 and milrinone improved the function of the acutely failing heart, as indicated by the increase in the values of the variables related to left ventricular function, but differences existed. The most striking differences were the normalization of the left ventricular external mechanical efficiency with R80122, but not with milrinone, and the maintenance of aortic blood pressure during infusion of R80122, which decreased during infusion of milrinone. Milrinone tends to induce ventricular tachycardia more frequently than R80122. It can be concluded that R80122 and milrinone improve the function of the acutely failing heart, but that the changes induced by R80122 are better balanced, i.e., enhancement of external mechanical efficiency with maintenance of aortic blood pressure.
[Effects of R80122. The influence of a new phosphodiesterase inhibitor on global and intestinal hemodynamics in coronary surgery patients]
Anaesthesist 1992 Aug;41(8):474-80.PMID:1524159doi
Phosphodiesterase III inhibitors have been established in recent years in the therapy of congestive heart failure. Many disadvantages, such as extensive vasodilation and the lack of proven positive inotropic properties combined with thrombepenia and elevation of transaminases, have complicated the handling of the drug in clinical practice. Enoximone, an imidazole derivative, has been demonstrated to be more cardioselective and vasodilation has been found to be less pronounced than with amrinone. As a consequence, research was performed to enhance the cardioselectivity of phosphodiesterase III inhibitors by reduction of non-specific cross-reactivity with other phosphodiesterases, and R80122 (Janssen Pharmaceutics, Belgium) was introduced into clinical practice. R80122 ((E)-Ncyclohexal-N-methyl-2[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1b]-quinazolin-7-yl)methylene] amino] oxy] acetamide) is a selective inhibitor of phosphodiesterase (PDE) IIIc, which is localized in the myocardium. Thus, its inhibition leads to a positive inotropic effect, whereas phosphodiesterase IIIRo is found in the vessel wall and causes vasodilation. This study was performed to investigate the hemodynamic profile of R80122 under clinical conditions. Additionally, the intestinal hemodynamics were recorded and changes in intestinal perfusion compared with changes in global hemodynamics. METHODS. The study was thoroughly discussed and approved by the local ethics committee; all patients gave written informed consent. The investigation was performed on ten male patients who were about to undergo elective coronary artery bypass surgery. History, physical examination and laboratory results were within the normal limits and revealed no evidence of liver disease. The usual medication was continued until the day before the operation. Premedication consisted of 2 mg flunitrazepam p.o. in the evening before the operation and 1.5 h before induction of anaesthesia. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. After induction of anaesthesia (MP1), after application of a bolus dose of R80122 (0.3 mg/kg BW) (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Anaesthesia was induced with a bolus dose of 0.2 mg/kg BW etomidate, 7 micrograms/kgBW fentanyl and 0.1 mg/kgBW pancuronium and maintained with a continuous infusion of 20 micrograms/min fentanyl, 300 micrograms/min midazolam and mechanical ventilation with O2/N2O at an FiO2 of 0.5. Statistical analysis was performed using the Wilcoxon-Mann-Whitney U test comparing the results after induction of anesthesia (MPI) with those after application of R80122 (MPII) and the results of MPII with those at sternotomy (MPIII). Statistical significance was assumed at P less than 0.05. RESULTS. After the induction of anaesthesia, the median heart rate (HR) was 56/min and did not change after administration of R80122. During sternotomy there was a significant increase in the HR from 64 to 78/min (P less than 0.05). Median arterial blood pressure (MAP) tended to decreased from 91 mm Hg after induction of 77 mm Hg after administration of R80122, although there was no statistical significance because of interindividual differences in the tendencies. At sternotomy, MAP remained unchanged. Cardiac output (CO) increased by 60% after administration of R80122 (P less than 0.01) and did not change during sternotomy. As a consequence of the changes in HR and CO, stroke volume (SV) increased by 22% after administration of R80122 (P less than 0.025) and decreased to control values during sternotomy.
Effects of R80122, a new phosphodiesterase inhibitor, on liver and global haemodynamics in patients undergoing coronary artery bypass surgery
Cardiovasc Surg 1994 Dec;2(6):698-702.PMID:7858987doi
R80122 (0.3 mg/kg body weight), a new phosphodiesterase inhibitor, was tested in ten patients undergoing coronary artery bypass surgery. Haemodynamic measurements were made and hepatic blood flow assessed by the indocyanine green infusion method using liver vein catheterization. Cardiac index increased by 63% and systemic vascular resistance decreased by 47%. Hepatic blood flow and intestinal vascular resistance were not significantly affected; nor was hepatic oxygen consumption. It is concluded that R80122 is a highly cardioselective phosphodiesterase inhibitor and that the reduction in systemic vascular resistance by this drug is not an effect of extensive intestinal vasodilatation.
[Hemodynamic effects of new phosphodiesterase inhibitors in patients with coronary heart disease. A comparison between enoximone and R80122]
Anaesthesist 1995 Jun;44(6):410-6.PMID:7653792DOI:10.1007/s001010050169.
At present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotropic and lusitropic effects, these drugs are still under discussion because of certain adverse effects like thrombopaenia, elevation of transaminases, abdominal disregulation, and excessive peripheral vasodilatation. As a consequence, more cardioselective phosphodiesterase inhibitors were developed with the aim of reducing these adverse effects. One of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole derivative, has nearly no influence on platelets and abdominal organ function. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig. 1), was developed. First experimental studies showed high cardioselectivity of this substance. The aim of this study was to compare the haemodynamic effects of enoximone and R80122 in patients with ischaemic heart disease. METHODS. This study was thoroughly discussed and approved by the local Ethics Committee; all patients gave written informed consent. Twenty male patients (Table 1) with normal left ventricular function who were about to undergo elective coronary artery bypass surgery were randomly allocated to receive a bolus of either 1.0 mg/kg enoximone or 0.3 mg/kg R80122 after induction of anaesthesia. Premedication consisted of 2 mg flunitrazepam orally the evening before and in the morning 1 h before operation. Anaesthesia was induced with 0.007 mg/kg fentanyl, 0.2 mg/kg etomidate, and 0.1 mg/kg pancuronium bromide and maintained by a continuous infusion of 0.02 mg/min fentanyl and 0.3 mg/min midazolam. After induction of anaesthesia haemodynamic measurements were performed and blood gas samples were taken preoperatively under steady-state conditions before and 5, 30, and 60 min after drug administration. RESULTS. The results of both groups are shown in Table 2 as mean values with standard deviations. Individual changes of cardiac index (CI), mean arterial pressure (MAP), and systemic vascular resistance (SVR) are depicted in Fig. 2. Peak percentage changes of the haemodynamic parameters are shown in Fig. 3. Both substances improved cardiac function; 5 min after drug administration CI increased by 31% and 26%, respectively. This was accompanied by increases in stroke volume (13% and 14%, respectively) and heart rate (15% and 10%, respectively). At the same time, there were declines in SVR (38% and 36%, respectively) and MAP (19% and 21%, respectively). Although mean values of pulmonary arterial and wedge pressure decreased after drug administration, these changes were inconsistent and not of clinical relevance. There were no statistically significant differences between the haemodynamic effects of both substances at any time in this study. CONCLUSIONS. Both enoximone and R80122 showed the expected inotropic effects. Nevertheless, both substances have a distinct vasodilative effect, which leads to a decline in MAP. R80122 does not have higher cardioselectivity than enoximone.