Summary: A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS.

Top Publications

  1. Muzandu K, Ishizuka M, Sakamoto K, Shaban Z, El Bohi K, Kazusaka A, et al. Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications. Toxicol Appl Pharmacol. 2006;215:330-40 pubmed
    ..5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo. ..
  2. Singh I, Sullivan P, Hall E. Peroxynitrite-mediated oxidative damage to brain mitochondria: Protective effects of peroxynitrite scavengers. J Neurosci Res. 2007;85:2216-23 pubmed
  3. Konishi K, Watanabe N, Arai T. SIN-1 cytotoxicity to PC12 cells is mediated by thiol-sensitive short-lived substances generated through SIN-1 decomposition in culture medium. Nitric Oxide. 2009;20:270-8 pubmed publisher
    ..These results suggest that SIN-1 cytotoxicity in PC12 cells is mediated via the generation of cytotoxic substances in the medium during its decomposition...
  4. Saito S, Yamamoto Katou A, Yoshioka H, Doke N, Kawakita K. Peroxynitrite generation and tyrosine nitration in defense responses in tobacco BY-2 cells. Plant Cell Physiol. 2006;47:689-97 pubmed
    ..These bands were also recognized in INF1-treated BY-2 cells and were found to be slightly suppressed by urate. Our study is the first to report ONOO(-) detection and tyrosine nitration in defense responses in plants. ..
  5. Klink M, Cedzynski M, St Swierzko A, Tchorzewski H, Sulowska Z. Involvement of nitric oxide donor compounds in the bactericidal activity of human neutrophils in vitro. J Med Microbiol. 2003;52:303-8 pubmed
    ..the presence of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), a molsidomine metabolite. SNP and molsidomine are drugs commonly used as nitrovasodilators in coronary heart disease...
  6. Kovanecz I, Rivera S, Nolazco G, Vernet D, Segura D, Gharib S, et al. Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage. J Sex Med. 2012;9:2814-26 pubmed publisher the BCNR model the effects of sildenafil at lower doses, alone or in combination with MDSC or the NO donor molsidomine, on CVOD and the underlying corporal histopathology...
  7. Rabkin S. Nitric oxide-induced cell death in the heart: the role of autophagy. Autophagy. 2007;3:347-9 pubmed
  8. Pitsikas N. The nitric oxide (NO) donor molsidomine antagonizes scopolamine and L-NAME-induced performance deficits in a spatial memory task in the rat. Behav Brain Res. 2009;200:160-4 pubmed
    ..The present study was designed to investigate the effects of the NO donor molsidomine on rats' spatial memory. Thus, the ability of molsidomine (2 and 4 mg/kg, i.p...
  9. Wohrle J, Hoher M, Nusser T, Hombach V, Kochs M. No effect of highly dosed nitric oxide donor molsidomine on the angiographic restenosis rate after percutaneous coronary angioplasty: a randomized, placebo controlled, double-blind trial. Can J Cardiol. 2003;19:495-500 pubmed
    ..To study the effect of the NO donor molsidomine at a high dose of 8 mg tid on angiographic restenosis rate in a randomized, placebo controlled, double-blind ..

More Information


  1. Chander V, Chopra K. Molsidomine, a nitric oxide donor and L-arginine protects against rhabdomyolysis-induced myoglobinuric acute renal failure. Biochim Biophys Acta. 2005;1723:208-14 pubmed
    ..This study was designed to investigate the effect of molsidomine and L-arginine in glycerol induced ARF in rats...
  2. Harnek J, Zoucas E, Sjuve R, Arner A, Ekblad E, Schou H, et al. Local infusion of the nitric oxide donor Sin-1 after angioplasty. Effects on intimal hyperplasia in porcine coronary arteries. Acta Radiol. 2003;44:395-402 pubmed
    ..The IF/actin ratio can be useful as an early marker of intimal hyperplasia. ..
  3. Thome U, Lazrak A, Chen L, Kirk M, Thomas M, Forman H, et al. Novel SIN-1 reactive intermediates modulate chloride secretion across murine airway cells. Free Radic Biol Med. 2003;35:662-75 pubmed
  4. Klink M, Tchorzewski H, Sulowska Z. Oxidative and adhesive responses of human neutrophils to nitrovasodilators in vitro: the role of protein kinases. Mediators Inflamm. 2003;12:345-53 pubmed
    Sodium nitroprusside (SNP) and molsidomine are used in the treatment of coronary heart disease...
  5. Yoon M, Jeong T, Park D, Xu M, Oh H, Song K, et al. Antioxidant effects of quinoline alkaloids and 2,4-di-tert-butylphenol isolated from Scolopendra subspinipes. Biol Pharm Bull. 2006;29:735-9 pubmed
    ..In addition, compounds 1-3 showed 1,1-diphenyl-2-picrylhydrasyl (DPPH) radical scavenging activity and compound 1 also exhibited metal chelating activity. ..
  6. Choi W, Youn Y, Han E, Lee C. Protective effect of 1-methylated beta-carbolines against 3-morpholinosydnonimine-induced mitochondrial damage and cell viability loss in PC12 cells. Neurochem Res. 2004;29:1807-16 pubmed
    ..This results in the inhibition of caspase-9 and -3 and apoptotic cell death in PC12 cells by suppressing the toxic actions of reactive oxygen and nitrogen species, including the GSH depletion. ..
  7. Daiber A, Schildknecht S, Müller J, Kamuf J, Bachschmid M, Ullrich V. Chemical model systems for cellular nitros(yl)ation reactions. Free Radic Biol Med. 2009;47:458-67 pubmed publisher
    ..NO/UO2-flux model could apply, providing conditions that allow either direct electrophilic substitution at a thiolate or S-nitros(yl)ation via transnitrosation from S-nitrosoglutathione. ..
  8. Zordan P, Sciorati C, Campana L, Cottone L, Clementi E, Querini P, et al. The nitric oxide-donor molsidomine modulates the innate inflammatory response in a mouse model of muscular dystrophy. Eur J Pharmacol. 2013;715:296-303 pubmed publisher
    ..We have investigated the immune-modulating effect of one of such drugs, molsidomine, able to slow the progression of muscular dystrophy in the ?-Sarcoglican-null mice, a model for the limb girdle ..
  9. Swintek A, Christoph S, Petrat F, de Groot H, Kirsch M. Cell type-dependent release of nitric oxide and/or reactive nitrogenoxide species from intracellular SIN-1: effects on cellular NAD(P)H. Biol Chem. 2004;385:639-48 pubmed
    ..Hence, care should be taken when applying SIN-1 as an exclusively peroxynitrite-generating compound in cell culture systems. ..
  10. Li C, Trudel L, Wogan G. Genotoxicity, mitochondrial damage, and apoptosis in human lymphoblastoid cells exposed to peroxynitrite generated from SIN-1. Chem Res Toxicol. 2002;15:527-35 pubmed
    SIN-1 (3-morpholinosydnonimine), the active metabolite of the vasodilator drug molsidomine, decomposes spontaneously in solution...
  11. Kaji T, Kaieda I, Hisatsune T, Kaminogawa S. 3-Morpholinosydnonimine hydrochloride induces p53-dependent apoptosis in murine primary neural cells: a critical role for p21(ras)-MAPK-p19(ARF) pathway. Nitric Oxide. 2002;6:125-34 pubmed
    ..Our findings clearly show that the p21(ras)-MAPK-p19(ARF) pathway has an essential role in p53-dependent apoptosis triggered by peroxynitrite in neural cells. ..
  12. Thomas S, Davies M, Stocker R. Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite. Chem Res Toxicol. 1998;11:484-94 pubmed
    ..The studies also highlight differences between ONOO-- and SIN-1-induced LDL oxidation with regards to the effects of bicarbonate, ascorbate, and urate. ..
  13. Trackey J, Uliasz T, Hewett S. SIN-1-induced cytotoxicity in mixed cortical cell culture: peroxynitrite-dependent and -independent induction of excitotoxic cell death. J Neurochem. 2001;79:445-55 pubmed
    ..Further, the mode of excitotoxicity by which injury progresses is determined by the NO-related species generated. ..
  14. Doulias P, Barbouti A, Galaris D, Ischiropoulos H. SIN-1-induced DNA damage in isolated human peripheral blood lymphocytes as assessed by single cell gel electrophoresis (comet assay). Free Radic Biol Med. 2001;30:679-85 pubmed
    ..The data suggest that H2O2-induced changes in Ca(2+) homeostasis are the predominant pathway for the induction of SSB in human lymphocytes exposed to oxidants. ..
  15. Pascual C, Reinhart K. Effect of antioxidants on induction time of luminol luminescence elicited by 3-morpholinosydnonimine (SIN-1). Luminescence. 1999;14:83-9 pubmed
    ..SIN-1 could be useful as a source of oxidant for the characterization of antioxidant behaviour in a system where superoxide and nitric oxide are simultaneously generated. ..
  16. Boykin J, BAYLIS C, Allen S, Humphries Y, Shawler L, Sommer V, et al. Treatment of elevated homocysteine to restore normal wound healing: a possible relationship between homocysteine, nitric oxide, and wound repair. Adv Skin Wound Care. 2005;18:297-300 pubmed
  17. Migita K, Maeda Y, Abiru S, Komori A, Yokoyama T, Takii Y, et al. Peroxynitrite-mediated matrix metalloproteinase-2 activation in human hepatic stellate cells. FEBS Lett. 2005;579:3119-25 pubmed
    ..These results suggest that peroxynitrite may contribute to the remodeling of the extracellular matrix in liver by activating pro-MMP-2. ..
  18. Klassen S, Rabkin S. Nitric oxide induces gene expression of Jumonji and retinoblastoma 2 protein while reducing expression of atrial natriuretic peptide precursor type B in cardiomyocytes. Folia Biol (Praha). 2008;54:65-70 pubmed
    ..These data suggest that JMJ may be a critical, previously unrecognized factor that mediates some of the cellular effects of NO, that NO may be able to increase JMJ in diseases associated with reduced JMJ expression. ..
  19. Hernández Melesio M, González Esquivel D, Ortiz Plata A, Sanchez Mendoza A, Sánchez García A, Alcaraz Zubeldia M, et al. Molsidomine modulates the cNOS activity in an experimental model of cholinergic damage induced by 192-IgG saporin. Neurosci Lett. 2011;491:133-7 pubmed publisher
    The aim of this work was to study the effect of molsidomine (MOLS), a nitric oxide (NO) donor, on the nitrergic system changes in an experimental model of cholinergic damage induced by 192 IgG saporin (SAP)...
  20. Yamauchi T, Kashii S, Yasuyoshi H, Zhang S, Honda Y, Akaike A. Mitochondrial ATP-sensitive potassium channel: a novel site for neuroprotection. Invest Ophthalmol Vis Sci. 2003;44:2750-6 pubmed
    ..It is suggested that opening of the Mit K (ATP) channel inhibited glutamate-induced generation of superoxide. ..
  21. Ho S, Chiu S, Hu T. Comparative kinetics of thiol oxidation in two distinct free-radical generating systems: SIN-1 versus AAPH. Free Radic Res. 2012;46:1190-200 pubmed publisher
    ..In conclusion, our study provides experimental and theoretical evidence that SIN-1 is mainly an one-electron oxidizing agent that can be functionally mimicked by AAPH. ..
  22. Tiago T, Simão S, Aureliano M, Martín Romero F, Gutierrez Merino C. Inhibition of skeletal muscle S1-myosin ATPase by peroxynitrite. Biochemistry. 2006;45:3794-804 pubmed
    ..V(1) to induce the intermediate catalytic transition state and also produced the partial unfolding of S1 that leads to an enhanced susceptibility of S1 to trypsin digestion, which can be fully protected by 2 mM GSH. ..
  23. Dokucu A, Ozturk H, Ozturk H, Tuncer M, Yilmaz F. The effects of molsidomine on hypoxia inducible factor alpha and Sonic hedgehog in testicular ischemia/reperfusion injury in rats. Int Urol Nephrol. 2009;41:101-8 pubmed publisher
    This study was designed to determine the effect of molsidomine (MO), a precursor of nitric oxide (NO) donor, on hypoxia inducible factor alpha (HIF-1alpha) and Sonic hedgehog (Shh) levels considered to be involved in the development of ..
  24. Carlo M, Loeser R. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum. 2003;48:3419-30 pubmed
    ..This may represent an important contributing factor to the development of osteoarthritis in older adults. ..
  25. Mak I, Weglicki W. Potent antioxidant properties of 4-hydroxyl-propranolol. J Pharmacol Exp Ther. 2004;308:85-90 pubmed
    ..Being a major metabolite in human and with its plasma level approaching that of propranolol, 4-HO-propranolol may contribute, in part, to the cardiovascular therapeutic benefits of propranolol. ..
  26. Ehlert A, Manthei G, Hesselmann V, Mathias K, Bein B, Pluta R. A Case of Hyperacute Onset of Vasospasm After Aneurysmal Subarachnoid Hemorrhage and Refractory Vasospasm Treated with Intravenous and Intraventricular Nitric Oxide: A Mini Review. World Neurosurg. 2016;91:673.e11-8 pubmed publisher
    ..A continuous intravenous molsidomine infusion was started and clinical stabilization was achieved for a week (Hunt and Hess grade I; World ..
  27. Rocchitta G, Migheli R, Mura M, Esposito G, Marchetti B, Desole M, et al. Role of endogenous melatonin in the oxidative homeostasis of the extracellular striatal compartment: a microdialysis study in PC12 cells in vitro and in the striatum of freely moving rats. J Pineal Res. 2005;39:409-18 pubmed
  28. Tanaka A, Nishida K, Okuda H, Nishiura T, Higashi Y, Fujimoto S, et al. Peroxynitrite treatment reduces adenosine uptake via the equilibrative nucleoside transporter in rat astrocytes. Neurosci Lett. 2011;498:52-6 pubmed publisher
    ..These findings suggest that under oxidative stress-loaded conditions, decreased adenosine clearance via astrocytic ENT1 might involve, at least in part, in an elevated extracellular adenosine level in the brain. ..
  29. Siegemund M, van Bommel J, Sinaasappel M, Schwarte L, Studer W, Girard T, et al. The NO donor SIN-1 improves intestinal-arterial P(CO(2)) gap in experimental endotoxemia: an animal study. Acta Anaesthesiol Scand. 2007;51:693-700 pubmed
    ..This finding is consistent with the concept that vasodilators may correct pathologic flow distribution within the intestinal wall. ..
  30. Lum P, Armour C, Stepaniants S, Cavet G, Wolf M, Butler J, et al. Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes. Cell. 2004;116:121-37 pubmed
    ..lanosterol synthase in the sterol biosynthetic pathway was identified as a target of the antianginal drug molsidomine, which may explain its cholesterol-lowering effects...
  31. Tao L, Jiao X, Gao E, Lau W, Yuan Y, Lopez B, et al. Nitrative inactivation of thioredoxin-1 and its role in postischemic myocardial apoptosis. Circulation. 2006;114:1395-402 pubmed
  32. Makohon N, Voznesens ka T, Bryzhina T, Sukhina V, Hrushka N, Aleksieieva I. [The protective effect of molsidomin in immune ovarian pathology in mice]. Fiziol Zh. 2007;53:29-34 pubmed
  33. Marvasi M, Durie I, Henríquez T, Satkute A, Matuszewska M, Prado R. Dispersal of human and plant pathogens biofilms via nitric oxide donors at 4 °C. AMB Express. 2016;6:49 pubmed publisher
    ..dispersion was mainly limited to Pectobacterium carotovorum biofilms, decreasing up to 15 % after exposure to molsidomine. Finally, the association of selected nitric oxide donors with sanitizers (DiQuat, H2O2, peracetic acid and ..
  34. Pellegrino D, Acierno R, Tota B. Control of cardiovascular function in the icefish Chionodraco hamatus: involvement of serotonin and nitric oxide. Comp Biochem Physiol A Mol Integr Physiol. 2003;134:471-80 pubmed
    ..In contrast, SNP produced a notable relaxation of the bulbus wall with a marked increase of its stiffness, as indicated by the increase of systolic and diastolic dP/dt max (23 and 104%, respectively). ..
  35. Shafiee M, Carbonneau M, Urban N, Descomps B, Leger C. Grape and grape seed extract capacities at protecting LDL against oxidation generated by Cu2+, AAPH or SIN-1 and at decreasing superoxide THP-1 cell production. A comparison to other extracts or compounds. Free Radic Res. 2003;37:573-84 pubmed
    ..e. cell-mediated) types of action in protecting LDL against oxidation, strengthening the need for improving the knowledge of its bioavailability in humans. ..
  36. Aman W, Thoma K. ICH guideline for photostability testing: aspects and directions for use. Pharmazie. 2003;58:877-80 pubmed
    ..may shorten testing times, but can lead to enforcement of photodegradation, which was demonstrated for molsidomine tablets...
  37. Akhter S, Green J, Root P, Thatcher G, Mutus B. Peroxynitrite and NO+ donors form colored nitrite adducts with sinapinic acid: potential applications. Nitric Oxide. 2003;8:214-21 pubmed
    ..In addition, the relatively high extinction coefficient of O-nitrososinapinic acid means that it could be utilized as an analyte for the spectroscopic detection of peroxynitrite or NO(+)-donors in the submicromolar range. ..
  38. Pitsikas N, Rigamonti A, Cella S, Muller E. The GABAB receptor and recognition memory: possible modulation of its behavioral effects by the nitrergic system. Neuroscience. 2003;118:1121-7 pubmed
    ..p.), counteracted these baclofen-induced performance deficits. The nitric oxide donor molsidomine, at the dose of 4 but not 2 mg/kg, i...
  39. Gutiérrez Martín Y, Martín Romero F, Henao F, Gutierrez Merino C. Alteration of cytosolic free calcium homeostasis by SIN-1: high sensitivity of L-type Ca2+ channels to extracellular oxidative/nitrosative stress in cerebellar granule cells. J Neurochem. 2005;92:973-89 pubmed
    ..5-1 microm/min, while higher concentrations of peroxynitrite and hydrogen peroxide are required for the inhibition of the plasma membrane Ca2+ ATPase and induction of necrotic cell death, respectively. ..
  40. Huang H, Zhang H, Ou H, Chen H, Gibson G. alpha-keto-beta-methyl-n-valeric acid diminishes reactive oxygen species and alters endoplasmic reticulum Ca(2+) stores. Free Radic Biol Med. 2004;37:1779-89 pubmed
    ..The same H(2)O(2)-induced ROS that reacts with KMV may also underlie the changes in BRCS related to AD. Thus, KMV ameliorates the effects of ROS on calcium homeostasis related to oxidative stress and to AD. ..
  41. Acquaviva R, Campisi A, Murabito P, Raciti G, Avola R, Mangiameli S, et al. Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism. Anesthesiology. 2004;101:1363-71 pubmed
  42. Peters H, Daig U, Martini S, Ruckert M, Schaper F, Liefeldt L, et al. NO mediates antifibrotic actions of L-arginine supplementation following induction of anti-thy1 glomerulonephritis. Kidney Int. 2003;64:509-18 pubmed
    ..nitro-L-arginine-methyl ester (L-NAME) in the drinking water]; and (5) GN-Molsi (10 mg/day of the NO donor molsidomine)...
  43. Chandra S, Romero M, Shatanawi A, Alkilany A, Caldwell R, Caldwell R. Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway. Br J Pharmacol. 2012;165:506-19 pubmed publisher
    ..Our data indicate that the oxidative species ONOO(-) and H(2) O(2) increase arginase activity/expression through PKC-mediated activation of RhoA/Rho kinase pathway. ..
  44. Ichikawa T, Sugiura H, Koarai A, Yanagisawa S, Kanda M, Hayata A, et al. Peroxynitrite augments fibroblast-mediated tissue remodeling via myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol. 2008;295:L800-8 pubmed publisher
    ..01) and inhibited by anti-TGF-beta antibody. These results suggest that RNS can affect the differentiation to myofibroblasts and excessive ECM production via a NF-kappaB-TGF-beta(1)-dependent pathway. ..
  45. Gupta A, Sharma S, Chopra K. Reversal of iron-induced nephrotoxicity in rats by molsidomine, a nitric oxide donor. Food Chem Toxicol. 2008;46:537-43 pubmed
    ..Present study was designed to investigate the effect of NO donor, molsidomine (Mol) and inducible NO synthase inhibitor (iNOS), aminoguanidine (AG) in Fe-NTA-induced renal toxicity...
  46. Di Matteo V, Pierucci M, Benigno A, Crescimanno G, Esposito E, Di Giovanni G. Involvement of nitric oxide in nigrostriatal dopaminergic system degeneration: a neurochemical study . Ann N Y Acad Sci. 2009;1155:309-15 pubmed publisher
    ..p.; n= 5) pretreatment significantly restored the striatal DA contents. Conversely, 40 mg/kg i.p. of molsidomine (MOL, n= 5), an NO donor, significantly worsened the neurodegeneration (n= 5) and completely counteracted the ..
  47. Nare B, Garraway L, Vickers T, Beverley S. PTR1-dependent synthesis of tetrahydrobiopterin contributes to oxidant susceptibility in the trypanosomatid protozoan parasite Leishmania major. Curr Genet. 2009;55:287-99 pubmed publisher
    ..Since the intracellular pteridine levels of Leishmania can be readily manipulated, these organisms offer a powerful setting for the dissection of pteridine-dependent oxidant susceptibility in higher eukaryotes...
  48. Lozano F, Cascajo C, García Sánchez E, Barros M, Garcia Criado F, Parreño F, et al. Bacterial translocation as a source of Dacron-graft contamination in experimental aortic operation: the importance of controlling SIRS. Surgery. 2006;140:83-92 pubmed
    ..We have attempted to ascertain whether the nitric oxide donor molsidomine prevents aortic graft contamination through control of the SIRS and a decrease in bacterial translocation (BT)...
  49. Hajlaoui N, Tarragano F, Raisky P, Beaufils P, Henry P. [Coronary spastic angina refractory to optimal medical therapy treated by angioplasty and stenting. A case report and review of literature]. Ann Cardiol Angeiol (Paris). 2010;59:103-6 pubmed publisher
    ..We propose also a review of the literature of the treatment of this pathology, which still remains not well codified. ..
  50. Lim S, Jang J, Na H, Lu S, Rahman I, Surh Y. 15-Deoxy-Delta12,14-prostaglandin J(2) protects against nitrosative PC12 cell death through up-regulation of intracellular glutathione synthesis. J Biol Chem. 2004;279:46263-70 pubmed
    ..The above findings suggest that 15d-PGJ(2) may act as a survival mediator capable of augmenting cellular thiol antioxidant capacity through up-regulation of the intracellular GSH synthesis in response to the nitrosative insult. ..
  51. Kina V, Villarreal C, Prado W. The effects of intraspinal L-NOARG or SIN-1 on the control by descending pathways of incisional pain in rats. Life Sci. 2005;76:1939-51 pubmed
  52. Osna N, Haorah J, Krutik V, Donohue T. Peroxynitrite alters the catalytic activity of rodent liver proteasome in vitro and in vivo. Hepatology. 2004;40:574-82 pubmed
    ..For in vivo experiments, mice were treated with molsidomine, which is metabolized to SIN-1 in liver...
  53. Hashitani H, Suzuki H. Properties of spontaneous Ca2+ transients recorded from interstitial cells of Cajal-like cells of the rabbit urethra in situ. J Physiol. 2007;583:505-19 pubmed
    ..ICC-LCs may not act as a coordinated pacemaker electrical network as do ICC in the gastrointestinal (GI) tract. Rather they may randomly increase excitability of USMCs to maintain the tone of urethral smooth muscles. ..