NSP-805
目录号 : GC32572
NSP-805是一种有效的，选择性的phosphodiesterase3(PDE3)抑制剂，为一种强心剂，具有舒张血管的作用。
Cas No.:125068-54-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
NSP-805 is a potent and selective inhibitor of guinea pig cardiac phosphodiesterase 3 (PDE3), and a cardiotonic agent with vasodilator properties.
In isolated guinea pig left atria, NSP-805 shows positive inotropic EC50 value in order of potency of 0.18 μM. The in vitro positive inotropic effects of NSP-805 is accompanied by increases in tissue cyclic AMP and abolished by carbachol[1].
In anesthetized dogs, intravenous (i.v.) injection of NSP-805 produces dose-dependent increases in left ventricular VVdp/dtmax and decreases in aortic blood pressure (ABP) with relatively small increases in heart rate (HR). The ED50 value for LVdP/dtmax of NSP-805 is 12 μg/kg. When the drugs is administered intraduodenally to anesthetized dogs, the ED50 value for LVdP/dtmax of NSP-805, is approximately 10 μg/kg. In the propranolol-induced heart failure model, NSP-805 completely improves the hemodynamic state of heart failure to normal levels[1]. NSP-805(100 μg/kg) reduces systemic blood pressure significantly, but the increase of chorio-retinal blood flow is less than that at the low dose of NSP-805 (40 μg/kg) in rabbit eyes[2].
[1]. Mochizuki N, et al. Cardiovascular effects of NSP-804 and NSP-805, novel cardiotonic agents with vasodilator properties. J Cardiovasc Pharmacol. 1993 Jun;21(6):983-95. [2]. Uchida H, et al. [The effect of phosphodiesterase type 3 inhibitor on chorio-retinal blood flow in rabbits eyes]. Nippon Ganka Gakkai Zasshi. 2002 Oct;106(10):615-20.
| Cas No. | 125068-54-4 | SDF | |
| Canonical SMILES | O=C1CC(C)C(C2=CC=C(NC3=C(C)C(CC3)=O)C=C2)=NN1 | ||
| 分子式 | C17H19N3O2 | 分子量 | 297.35 |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.363 mL | 16.8152 mL | 33.6304 mL |
| 5 mM | 0.6726 mL | 3.363 mL | 6.7261 mL |
| 10 mM | 0.3363 mL | 1.6815 mL | 3.363 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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。
Cardiovascular effects of NSP-804 and NSP-805, novel cardiotonic agents with vasodilator properties
J Cardiovasc Pharmacol 1993 Jun;21(6):983-95.PMID:7687727DOI:10.1097/00005344-199306000-00021.
The cardiovascular properties of NSP-804 (4,5-dihydro-6-[4-[(2-methyl-3-oxo-1-cyclopentenyl)-amino] phenyl]-3(2H)-pyridazinone) and NSP-805 (4,5-dihydro-5-methyl-6-[4-[(2-methyl-3-oxo-1-cyclopentenyl) amino]phenyl]-3(2H)-pyridazinone), novel cardiotonic agents, were investigated in vitro and in vivo in comparison with those of other cardiotonic agents. In isolated guinea pig left atria, the positive inotropic EC50 values (microM) in order of potency were about 0.18 (NSP-805), 0.39 (indolidan), 1.1 (MCI-154), 1.7 (NSP-804, milrinone), 2.0 (denopamine), 4.0 (papaverine), 4.4 3-isobutyl-1-methylxanthine, IBMX, 6.5 (imazodan), and 27 (amrinone). In anesthetized dogs, intravenous (i.v.) injection of NSP-804 and NSP-805 produced dose-dependent increases in left ventricular VVdp/dtmax and decreases in aortic blood pressure (ABP) with relatively small increases in heart rate (HR). The ED50 values (micrograms/kg) for LVdP/dtmax of NSP-804, NSP-805, denopamine, milrinone, MCI-154, and indolidan were 15, 12, 22, 23, 15, and 7.3, respectively. When the drugs were administered intraduodenally to anesthetized dogs, the ED50 values (micrograms/kg) for LVdP/dtmax of NSP-804, NSP-805, milrinone and indolidan were approximately 30, 10, 200, and 25 respectively. In the propranolol-induced heart failure model, NSP-804 and NSP-805 completely improved the hemodynamic state of heart failure to normal levels. The in vitro positive inotropic effects of NSP-804 and NSP-805 were accompanied by increases in tissue cyclic AMP and abolished by carbachol. NSP-805 was the most potent and selective inhibitor of guinea pig cardiac phosphodiesterase (PDE) III among the agents examined, and NSP-804 was a potent and selective inhibitor of PDE III similar to indolidan. The cardiovascular properties determined in this study suggest that both NSP-804 and NSP-805 may have beneficial effects for treatment of congestive heart failure (CHF).
[The effect of phosphodiesterase type 3 inhibitor on chorio-retinal blood flow in rabbits eyes]
Nippon Ganka Gakkai Zasshi 2002 Oct;106(10):615-20.PMID:12420371doi
Purpose: To investigate the ocular effect of intravenous administration of a phosphodiesterase type 3 inhibitor (NSP-805) and to compare the effect of NSP-805 with that of a calcium antagonist (nicardipine hydrochloride) on chorio-retinal blood flow in anesthetized albino rabbits. Methods: Twenty-four female albino rabbits (weighting 2.0-4.0 kg) were anesthetized with intravenous injection. NSP-805(40 micrograms/kg and 100 micrograms/kg) and nicardipine of 40 micrograms/kg were intravenously administrated to the anesthetized rabbits. Intravenously administration of 20% dimethyl sulfoxide (DMSO) was used as a vehicle. Chorio-retinal blood flow was measured with a laser Doppler flowmeter at baseline and every 20 minutes after intravenous administration for 120 minutes. Heart rates and systemic blood pressure were monitored. Baseline measurements were compared with every 10 minutes after intravenous administration. Differences between the drug groups and vehicle group were analyzed. Results: After administration of a low dose of NSP--805 (40 micrograms/kg) and nicardipine (40 micrograms/kg), the chorio-retinal blood flow was significantly increased (p < 0.05). A high dose NSP-805(100 micrograms/kg) reduced systemic blood pressure significantly, but the increase of chorio-retinal blood flow was less than that at the low dose of NSP-805(40 micrograms/kg) and nicardipine (40 micrograms/kg). Chorio-retinal blood flow in the NSP 805(40 micrograms/kg) and nicardipine (40 micrograms/kg) groups was significantly increased over that in the control group (20% DMSO) (p < 0.05). Conclusion: The results suggest that the NSP-805 has the potential of increasing chorio-retinal blood flow in rabbit eyes.
Identification and characterization of isoenzymes of cyclic nucleotide phosphodiesterase in human kidney and heart, and the effects of new cardiotonic agents on these isoenzymes
Naunyn Schmiedebergs Arch Pharmacol 1994 Sep;350(3):284-93.PMID:7824045DOI:10.1007/BF00175034.
The present study was done to identify and characterize the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) and to determine their intracellular distribution in human kidney and heart. The in vitro effects of new cardiotonic agents, namely, NSP-805 (4,5-dihydro-5-methyl-6-[4-[(2-methyl-3-oxo-1-cyclopentenyl)amino] phenyl]-3(2H)-pyridazinone), TZC-5665 (6-[4-[2-[3-(5-chloro-2-cyanophenoxy)-2-hydroxypropylamino]- 2 -methylpropylamino]phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone ) and its metabolites, OPC-18790 ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2 -hydroxypropoxy]-2-(1H)-quinolinone), MS-857 (4-acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone ) and E-1020 (1,2-dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate), on these human PDE isoenzymes were also investigated. PDE isoenzymes were separated from cytosolic and particulate fractions of homogenates of human kidney and heart by DEAE-Sepharose chromatography. PDE isoenzymes were identified by their elution characteristics, substrate specificities, sensitivities to regulation by effectors and by the use of isoenzyme-specific inhibitors. In a cytosolic fraction from kidney, Ca2+/calmodulin-dependent PDE (CaM-PDE), cyclic GMP-stimulated PDE (cGS-PDE), cyclic GMP-inhibited PDE (cGI-PDE) and two forms of cyclic AMP-specific PDE (cAMP-PDE) were resolved. One form of cAMP-PDE (cAMP-PDE alpha), which was eluted at a lower ionic strength than cGI-PDE during DEAE-Sepharose chromatography, was newly recognized in human tissues, though the other form (cAMP-PDE beta), which eluted later than cGI-PDE, had been previously isolated.(ABSTRACT TRUNCATED AT 250 WORDS)