Disease relevance of Lopac-M-184

• Inducibly expressed luciferase activity in hypoxia was inhibited by the addition of SNP and two other structurally different NO donors, S-nitroso-L-glutathione and 3-morpholinosydnonimine, giving IC50 values of 7.8, 211, and 490 microM, respectively [1].
• However, bone resorption depends on precursor replication and on the activity of the mature cells, and we found that the NO donor 3-morpholinosydnonimine (SIN-1) (50 microM) profoundly depressed replication in the human preosteoclast line [2].
• Here we show that both authentic peroxynitrite and SIN-1 (3-morpholinosydnonimine hydrochloride), a molecule that decomposes into NO and to form peroxynitrite, can inhibit wild-type p53 function in malignant glioma cells [3].
• The effects of linsidomine on portal hypertension [4].
• These findings show that at the early phase of an endotoxin shock, and in the absence of intense fluid resuscitation, linsidomine perfusion is beneficial in maintaining systemic and hepatic perfusion while preventing lactic acidosis [5].

Psychiatry related information on Lopac-M-184

• Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction [6].

High impact information on Lopac-M-184

• Authentic NO gas as well as the NO-generating compound 3-morpholinosydnonimine (SIN-1) also conversely modulated aconitase and IRE binding activities of purified recombinant IRF [7].
• Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the .NO and O2.- generator SIN-1 (3-morpholinosydnonimine) was inhibited more effectively by gammaT than alphaT [8].
• METHODS AND RESULTS: In a prospective multicenter, randomized trial, 700 stable coronary patients scheduled for angioplasty received direct NO donors (infusion of linsidomine followed by oral molsidomine) or oral diltiazem [9].
• Effect of the direct nitric oxide donors linsidomine and molsidomine on angiographic restenosis after coronary balloon angioplasty. The ACCORD Study. Angioplastic Coronaire Corvasal Diltiazem [9].
• In vitro treatment of hepatic microsomes with NO, produced by chemical decomposition of 3-morpholinosydnonimine or by nitric oxide synthase, substantially suppressed cytochrome P450-dependent oxygenation reactions [10].

Chemical compound and disease context of Lopac-M-184

• Because nitric oxide (NO.) is suggested to be cytoprotective, we examined the effects of nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) on MPP+-induced toxicity in astrocytes [11].
• We conducted a prospective, randomized, multicentre, parallel group, single-blind study to compare the efficacy of intravenous administration of linsidomine with that of isosorbide dinitrate in unstable angina [12].
• In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, inhibited virus replication only to a very low extent in vitro, but pretreatment of virus with SIN-1 led to a considerably lowered viability of the virions [13].
• As peroxynitrite is implicated as an oxidant for low-density lipoprotein (LDL) in atherogenesis, we investigated this process using reagent peroxynitrite (ONOO-) and 3-morpholinosydnonimine (SIN-1, which produces peroxynitrite via generation of NO. and O2.-) [14].
• DHEA, however, did not protect glucose-deprived C6 glioma cells from the exogenously produced peroxynitrite by 3-morpholinosydnonimine [15].

Biological context of Lopac-M-184

• Therefore, we determined the effect of an exogenous NO donator, sin-1 (3-morpholinosydnonimine), on canine and human LTMCs and on apoptosis [16].
• In vitro, CLHb abolished the inhibitory effect of the NO donor 3-morpholinosydnonimine on platelet aggregation and enhanced the aggregation of stimulated but not resting platelets [17].
• We conclude that linsidomine decreases portal venous pressure by reducing portocollateral resistances without affecting liver blood flow [18].
• Cultured mouse astrocytes were treated with the cytotoxic concentrations of N-methyl-N'-nitro-N-nitrosoguanidine or 3-morpholinosydnonimine to induce DNA damage and PARP-1 activation [19].
• Radioimmunoassay measurement of insulin release and a dynamic assay of exocytosis using the dye FM1-43 demonstrated that three different NO donors-hydroxylamine (HA), sodium nitroprusside, and 3-morpholinosydnonimine (SIN-1)-each stimulated a marked increase in insulin secretion from INS-1 cells [20].

Anatomical context of Lopac-M-184

• Coronary diameter changes of the proximal and midportion of the left anterior descending coronary artery were assessed by quantitative coronary angiography during rapid atrial pacing, cold pressor test, supine exercise, and subselective infusion of papaverine and after intracoronary injection of linsidomine (SIN-1) [21].
• Neither the capacity of the endothelial cells to form NO in response to the calcium ionophore A23187 nor the capacity of the underlying smooth muscle cells to relax in response to sources of exogenous NO (3-morpholinosydnonimine and nitroglycerin) was affected by the neointima [22].
• Nitroglycerin (10(-5) M) and the active metabolite of molsidomine, 3-morpholinosydnonimine (10(-5) M), did not modify the basal production of endothelin from the intima of intact porcine aortas [23].
• We therefore studied the sensitivity of fibroblasts from patients with sporadic ALS (SALS), and from patients with familial ALS (FALS) associated with copper/zinc superoxide dismutase (Cu/ZnSOD) mutations (SOD1-FALS), to the free radical-generating agents 3-morpholinosydnonimine (SIN-1) and hydrogen peroxide (H2O2), and to serum withdrawal [24].
• The present study investigates the effect of nitroxides on the detectable amount of .NO released by 3-morpholinosydnonimine (SIN-1) and cultured endothelial cells [25].

Associations of Lopac-M-184 with other chemical compounds

• CONCLUSIONS: Treatment with linsidomine and molsidomine was associated with a modest improvement in the long-term angiographic result after angioplasty but had no effect on clinical outcome [9].
• When NO was generated by 3-morpholinosydnonimine hydrochloride in the presence of SOD, NO- or a similar reductant was formed, which reduced catalase compound II and promoted the formation of the catalase [Fe(III)]-NO complex [26].
• Three NO donors, 3-morpholinosydnonimine (SIN-1, 0.1 mmol/L), S-nitroso-acetylcysteine (0.1 mmol/L), and sodium nitroprusside (0.1 mmol/L), suppressed the beta-adrenergic agonist isoproterenol (ISO, 1 mumol/L)-stimulated increase in ICa-L [27].
• Treatment of ECs with an NO donor, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1), inhibited this shear stress-induced Egr-1 expression [28].
• Using a highly selective antibody against cGMP in formaldehyde-fixed tissue, the NO donors SNP, 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-DL-penicillamine (SNAP) caused a strong increase in cGMP formation when applied under the same conditions as used for the electrophysiological recordings [29].

Gene context of Lopac-M-184

• We show here that exposure of MCF7 cells to physiological concentrations of peroxynitrite and to a peroxynitrite generator (3-morpholinosydnonimine N-ethylcarbamide, or SIN1) leads to the irreversible inactivation of NAT1 in cells [30].
• In a human glioblastoma cell line, T98G, treatment with any of three types of NO donors--sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-L-glutathione--caused a significant increase in the levels of heme oxygenase-1 mRNA but not in the levels of heme oxygenase-2 and heat-shock protein 70 mRNAs [31].
• A type II change (red shift) of the Soret band (405 nm --> 413-419 nm) was observed when wild-type HO-2 was treated with sodium nitroprusside (SNP), S-nitroglutathione (GSNO), S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1); the NO scavenger, hydroxocobalamin (HCB) prevented the shift [32].
• Addition of NO donors (3-morpholinosydnonimine (Sin-1), sodium nitroprusside, or S-nitrosoglutathione) reversed the effects of L-NMMA, confirming the role of NO on Cox-2 expression [33].
• 3. The blocking effects of NO released by SNAP, 3-morpholinosydnonimine (SIN-1; 1 mM), and 3-[2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propanamin e (NOC-5; 100 microM) on currents mediated by recombinant NRI/NR2B receptors were virtually indistinguishable from those observed on native receptors [34].

Analytical, diagnostic and therapeutic context of Lopac-M-184

• Fifteen animals were treated with saline solution (10 mL/hr) or linsidomine perfusion (2 mg over 3 hours, 10 mL/hr) [5].
• Only 25% of the patients had at least one episode of chest pain during the study (24.6% vs 25.8% in the linsidomine and isosorbide dinitrate groups, P = 0.74), of which 12% were associated with ECG changes [12].
• Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina. A French multicentre study. French Group of Investigators [12].
• Here, we show that dopaminergic neurons in midbrain-striatum co-cultures also exhibit resistance to the cytotoxicity of nitric oxide donors, 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC-18) and 3-morpholinosydnonimine (SIN-1) [35].
• The NO level within the spinal dorsal horn was increased by microdialysis of a NO donor, 3-morpholinosydnonimine (SIN-1) [36].

References