Molsidomine (SIN-10)
(Synonyms: 吗多明; SIN-10; Morsydomine) 目录号 : GC32579
An NO-
Cas No.:25717-80-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Molsidomine is a NO-
1.Nitz, R.E., and Fiedler, V.Molsidomine: Alternative approaches to treat myocardial ischemiaPharmacotherapy728-37(1987) 2.Rosenkranz, B., Winkelmann, B.R., and Parnham, M.J.Clinical pharmacokinetics of molsidomineClin. Pharmacokinet.30(5)372-384(1996)
| Cas No. | 25717-80-0 | SDF | |
| 别名 | 吗多明; SIN-10; Morsydomine | ||
| Canonical SMILES | O=C([N-]C1=C[N+](N2CCOCC2)=NO1)OCC | ||
| 分子式 | C9H14N4O4 | 分子量 | 242.23 |
| 溶解度 | DMSO : ≥ 42 mg/mL (173.39 mM) | 储存条件 | Store at -20°C,protect from light |
| 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 | 4.1283 mL | 20.6415 mL | 41.2831 mL |
| 5 mM | 0.8257 mL | 4.1283 mL | 8.2566 mL |
| 10 mM | 0.4128 mL | 2.0642 mL | 4.1283 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。
Heterocyclic NO prodrugs
Farmaco 1999 May 30;54(5):316-20.PMID:10418124DOI:10.1016/s0014-827x(99)00031-2.
An overview of the different heterocyclic NO-releasing compounds is given. Mesoionic heterocycles like sydnone imines are one example. This class is discussed on the synthesis and the mechanism of NO formation from Molsidomine and its first metabolite SIN-1. Furthermore, 1,2,3,4 oxatriazolium olates and imidates are presented in an example of the synthesis of GEA-3175. Heterocyclic N-oxides are another group of compounds capable of NO release under certain conditions. This class is discussed in the example of furoxane carboxamides like CAS-1609, and some SAR-data show the great impact of intramolecular hydrogen bridges on their in vitro activity. Each class of compounds requires different cofactors for NO release: sydnone imines need oxidants like oxygen, furoxanes are converted to NO via reaction with thioles.
Pharmacokinetics of Molsidomine and of its active metabolite, SIN-1 (or linsidomine), in the elderly
Fundam Clin Pharmacol 1991;5(6):549-56.PMID:1955198DOI:10.1111/j.1472-8206.1991.tb00741.x.
The pharmacokinetics of Molsidomine were investigated in six young (25.5 +/- 0.6 years) and in six elderly healthy volunteers (81.1 +/- 3.1 years). After a 2 mg oral administration, Molsidomine elimination half-life was prolonged in elderly subjects (1.9 +/- 0.2 h versus 1.2 +/- 0.1 h, P less than 0.05) because of a decrease in its plasma clearance (15.1 +/- 3.2 l.h-1 versus 41.8 +/- 2.5 l.h-1 (P less than 0.01) in young volunteers). The elimination half-life of the active metabolite, SIN-1 or linsidomine was also prolonged in elderly subjects (1.8 +/- 0.2 h versus 1.0 +/- 0.08 h, P less than 0.05). AUCs of both Molsidomine and SIN-1 were increased in the elderly subjects, but the increase in the former was greater (x 3.4) than the increase in the latter (x 1.6). These results suggest that pharmacokinetics and metabolism of Molsidomine are impaired in elderly subjects.
Oxidative/Nitrative Mechanism of Molsidomine Mitotoxicity Assayed by the Cytochrome c Reaction with SIN-1 in Models of Biological Membranes
Chem Res Toxicol 2020 Nov 16;33(11):2775-2784.PMID:32706246DOI:10.1021/acs.chemrestox.0c00122.
Molsidomine is currently used as a vasodilator drug for the treatment of myocardial ischemic syndrome and congestive heart failure, although still presenting some mitochondrial-targeted side effects in many human cells. As a model of Molsidomine mitotoxicity, the reaction of cytochrome c with phosphatidylserine (PS)- and cardiolipin (CL)-containing liposomes was investigated in oxidative/nitrosative conditions imposed by SIN-1 decomposition, which renders peroxynitrite (ONOO-) as a main reactive product. In these conditions, the production of thiobarbituric acid-reactive substance (TBARs) and LOOH was affected by the lipid composition and the oxidative/nitrative conditions used. The oxidative/nitrative conditions were the exposure of lipids to SIN-1 decomposition, native cytochrome c after previous exposure to SIN-1, concomitantly to SIN-1 and native cytochrome c, native cytochrome c, and cytochrome c modified by SIN-1 that presents a less-rhombic heme iron (L-R cytc). TBARs and LOOH production by lipids and cytochrome c exposed concomitantly to SIN-1 differed from that obtained using L-R cytc and featured similar effects of SIN-1 alone. This result suggests that lipids rather than cytochrome c are the main targets for oxidation and nitration during SIN-1 decomposition. PS- and CL-containing liposomes challenged by SIN-1 were analyzed by Fourier transform infrared spectroscopy that revealed oxidation, trans-isomerization, and nitration. These products are consistent with reaction routes involving lipids and NOx formed via peroxynitrite or direct reaction of NO• with molecular oxygen that attacks LOOH and leads to the formation of substances that are not reactive with thiobarbituric acid.
Dynamics of Irreversible NO Release from Photoexcited Molsidomine
J Phys Chem Lett 2023 Jan 19;14(2):516-523.PMID:36626829DOI:10.1021/acs.jpclett.2c03613.
Molsidomine (SIN-10), an orally administered NO-delivery drug for vasodilation, cannot be used to alleviate hypertensive crisis because it releases NO at a slow rate. SIN-10 may be used to treat sudden cardiac abnormalities if the rapid and immediate release of NO is achieved via photoactivation. The photodissociation dynamics associated with the NO release process from SIN-10 in CHCl3 was investigated using time-resolved infrared spectroscopy. Approximately 41% of photoexcited SIN-10 at 360 nm decomposed into CO2, CH2CH3 radical, and the remaining radical fragment [SIN-1A(-H)] with a time constant of 43 ps. All SIN-1A(-H) released NO spontaneously with a time constant of 68 ns, becoming N-morpholino-aminoacetonitrile, resulting in 41% for the quantum yield of immediate NO release from SIN-10. The results obtained can be used to realize the quantitative control of the NO administration at a specific time, and SIN-10 can be potentially used to address the phenomenon of hypertensive crisis.
The effects of the nitric oxide donors Molsidomine and SIN-I on human polymorphonuclear leucocyte function in vitro and ex vivo
Eur J Clin Pharmacol 1992;43(6):629-33.PMID:1337322DOI:10.1007/BF02284962.
The nitrovasodilator and nitric oxide donor Molsidomine and its metabolite SIN-I dilate vascular smooth muscle and inhibit platelet activation by increasing intracellular concentrations of cyclic GMP. We have therefore studied the effects of Molsidomine and SIN-I on isolated human polymorphonuclear leucocytes (PMN) in vitro and ex vivo. In vitro Molsidomine dose-dependently reduced beta-glucuronidase release and the generation of superoxide anions from non-activated and from FMLP- or PAF-stimulated human PMNs. SIN-I was equally effective in reducing beta-glucuronidase release and totally inhibited oxygen radical generation at a concentration of 580 mumol.l-1. In a double-blind, placebo-controlled, randomized trial we also studied beta-glucuronidase release and the generation of superoxide anions from isolated PMNs. Blood was drawn from 12 healthy volunteers before and 3 h after oral Molsidomine (16 mg) or placebo. There was no statistically significant difference in beta-glucuronidase release and superoxide anion formation when the PMNs were isolated before or after Molsidomine or placebo. This was the case for non-activated, as well as FMLP- or PAF-stimulated PMNs. Thus, the nitric oxide donors Molsidomine and its metabolite SIN-I caused a dose-dependent inhibition of PMN functions in vitro, but no significant inhibition when the PMNs were isolated after oral Molsidomine.