ICI 153110
目录号 : GC32643
ICI153110是一种口服有效的磷酸二酯酶抑制剂，具有血管舒张和收缩力性质，可用于治疗充血性心力衰竭。
Cas No.:87164-90-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Alderley Park APfSD rats are used in this study. In all, 150 male rats and 150 female rats are assigned to four groups (one control and three treatment) in the two separate studies; 30 per sex representing the main (regular) test groups and 15 per sex for investigating reversibility of effects following treatment at the highest dose employed (withdrawal studies). The dose levels are 5, 10, and 250 mg/kg/day of ICI 153110. All animals are dosed orally, by gavage, using a plastic syringe and a flexible catheter. Equal numbers of animals per sex in the four groups are necropsied necropsied at each of two time points; following at least 28 consecutive days dosing (1 month) and 182 consecutive days of dosing (6 months). All animals are observed at least twice daily for any abnormal signs, all of which are recorded. Body weights, food consumption, water consumption, clinical pathology, and pharmacokinetics are also measured[1]. |
References: [1]. Westwood FR, et al. Pathologic changes in blood vessels following administration of an inotropic vasodilator (ICI 153,110) to the rat. Fundam Appl Toxicol. 1990 May;14(4):797-809. | |
ICI 153110 is an orally active phosphodiesterase inhibitor with both vasodilating and inotropic properties which is designed for the treatment of congestive cardiac failure.
ICI 153110 is an orally active phosphodiesterase inhibitor with both vasodilating and inotropic properties which is designed for the treatment of congestive cardiac failure. Fourteen animals have died as a direct or indirect consequence of ICI 153110 administration in the high-dose main test and reversibility groups. In the female rat dosed at 10 mg/kg/day ICI 153110 a mild focal arteritis is characterized by a predominantly and diffusely adventitial infiltration of mixed cells and early formation of fibrous tissue. The two rats dosed at 250 mg/kg/day ICI 153110 die prematurely from intratracheal intubation of dosing solution. Arteries from two further animals (dosed at 5 and 250 mg/kg/day ICI 153110) show minimal focal arteritis with medial necrosis, and medial and adventitial inflammation[1].
[1]. Westwood FR, et al. Pathologic changes in blood vessels following administration of an inotropic vasodilator (ICI 153,110) to the rat. Fundam Appl Toxicol. 1990 May;14(4):797-809.
| Cas No. | 87164-90-7 | SDF | |
| Canonical SMILES | O=C1CCC(/C=C/C2=CC=NC=C2)=NN1 | ||
| 分子式 | C11H11N3O | 分子量 | 201.22 |
| 溶解度 | Soluble in DMSO | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.9697 mL | 24.8484 mL | 49.6968 mL |
| 5 mM | 0.9939 mL | 4.9697 mL | 9.9394 mL |
| 10 mM | 0.497 mL | 2.4848 mL | 4.9697 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Long-term effects of an inotropic phosphodiesterase inhibitor (ICI 153,110) on the rat salivary gland, harderian gland, and intestinal mucosa
Toxicol Pathol 1991;19(3):214-23.PMID:1780638DOI:10.1177/019262339101900303.
The inotropic vasodilator, ICI 153,110, a phosphodiesterase inhibitor intended for the treatment of congestive heart failure, was administered to Alderley Park Wistar-derived rats for periods of up to 182 days. Treatment produced hypertrophy of salivary glands, hyperplasia of intestinal mucosa, and dacryoadenitis of the harderian gland. As the functions of these glandular tissues can be modified by factors which alter cyclic nucleotide metabolism, it is postulated that the glandular alterations produced by ICI 153,110 occurred as a result of phosphodiesterase inhibition.
Pathologic changes in blood vessels following administration of an inotropic vasodilator (ICI 153,110) to the rat
Fundam Appl Toxicol 1990 May;14(4):797-809.PMID:2361578DOI:10.1016/0272-0590(90)90304-3.
ICI 153,110 is an inotropic vasodilator compound intended for the treatment of congestive heart failure. It was administered to rats at dose levels of 5, 10, and 250 mg/kg/day for up to 6 months as part of its preclinical development program. Detailed clinical investigations were conducted during the course of the study and histopathological examination took place after 28 days and 182 days of treatment as well as 42 days following cessation of dosing. Changes were identified in blood vessels in the greater proportion of animals from the high dose group, although some of the changes were also observed at lower dose levels. Vascular tissues from a variety of sites were affected, particularly those of the mesentery, splanchnum, heart, testis, and the pampiniform plexus. Early changes characteristic of acute injury such as arterial medial necrosis and inflammation occurred, which were distinguishable from those following chronic administration of the compound where there was a pronounced arterial and venous wall thickening and accompanying plexiform vasculopathy. The essential components contributing to the thickening were a smooth muscle hypertrophy and hyperplasia of the media. At the end of the period following withdrawal of dosing, vascular thickening was still present and arteritis showed an increased incidence relative to that seen at termination of the main test. Systemic hypertension was not detected during these studies. Vasodilation occurring at or near normal blood pressure, resulting in breakdown of vascular autoregulation and excessive critical wall tension, may have been the cause of the pathological changes. Our findings indicate that medial necrosis is an early component in a sequence of adaptive, destructive, and reparative changes not only following a chemically induced perturbation of the hemodynamic status in arteries and veins but also following a shift back to the "normal state" on withdrawal of compound.
Acute neurohormonal and hemodynamic response to a new peak III phosphodiesterase inhibitor (ICI 153,110) in patients with chronic heart failure
J Cardiovasc Pharmacol 1990 Sep;16(3):360-6.PMID:1700205DOI:10.1097/00005344-199009000-00003.
Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.
Different inhibition and induction profiles of hepatic drug metabolism in rats and dogs by two structurally related pyridyl diazinone cardiotonic agents
Biochem Pharmacol 1991 Feb 1;41(3):411-7.PMID:1994899DOI:10.1016/0006-2952(91)90538-g.
ICI 153,110 and ICI 170,777, two pyridyl diazinone cardiotonic agents, produced a different profile of effects on hepatic microsomal mixed function oxidase enzymes following multiple oral dosing to rats and dogs; these differences may be related to the molecular dimensions of the two molecules. ICI 153,110 significantly increased levels of total P450, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase in rat microsomes, indicating an induction profile (P448) similar to that of beta-naphthoflavone. This was supported by gel electrophoresis (SDS-PAGE) of microsomal proteins; a similar type of induction was observed in dog microsomes. In contrast, ICI 170,777 produced no changes indicating enzyme induction in either rat or dog. Instead, ICI 170,777 appeared to inhibit specifically the activity of aldrin epoxidase in the rat. Inhibitory activity was also indicated in the rat by prolongation of pentobarbitone sleeping time following single oral doses of either ICI 153,110 or ICI 170,777. The time-course of this effect appeared to correlate more closely with the profile of circulating metabolites, although both parent compounds were found to produce type II spectral changes on interaction with control rat microsomes. The molecular dimensions (area/depth2) of the compounds supported the finding that only ICI 153,110 should interact with or induce P448 isozymes.