Disease relevance of Nitecapone

• The combined results suggest that the COMT-inhibitory and antioxidant properties of nitecapone provide a protective therapy against the development of diabetic nephropathy [1].
• Hyperfiltration, focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but in a manner that is more readily attributed to the antioxidant potential of the agent [1].
• Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6-fluorodopa [2].
• In the present study, the influence of nitecapone on isolated rat heart ischemia-reperfusion injury was investigated to elucidate its cardioprotective role [3].
• Behaviorally DM induced mechanical hypersensitivity that was markedly attenuated by oral treatment with nitecapone [4].

High impact information on Nitecapone

• This study was undertaken to investigate the effect of intraluminal nitecapone, a peripherally acting COMT inhibitor, on duodenal mucosal bicarbonate secretion in humans and to compare the effect with that of the prostaglandin E1 analogue misoprostol [5].
• A pattern of elevated oxidative stress, measured as CuZn superoxide dismutase gene expression and thiobarbituric acid-reactive substance content, was noted in diabetic rats, and both parameters were normalized by nitecapone treatment [1].
• We studied in vitro the ability of nitecapone, 3-[(3,4-dihydroxy-5-nitrophenyl)methylene]-2,4-pentanedione, a novel water-soluble compound with antioxidative properties, to inhibit the LDL oxidation promoted by copper ions, the aqueous free radical generator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), and mouse peritoneal macrophages [6].
• Nitecapone [3-(3,4-dihydroxy-5-nitrophenyl)methylene-2,4-pentanedione] [OR-462] is a catechol-O-methyltransferase inhibitor with gastroprotective properties [7].
• [18F]-6-fluorodopa PET scanning in Parkinson's disease after selective COMT inhibition with nitecapone (OR-462) [2].

Chemical compound and disease context of Nitecapone

• Reduction of circulating 3-O-methyldopa by inhibition of catechol-O-methyltransferase with OR-611 and OR-462 in cynomolgus monkeys: implications for the treatment of Parkinson's disease [8].
• Inhibition of gastric mucosal laminin receptor by Helicobacter pylori lipopolysaccharide: effect of nitecapone [9].
• 3. Ethanol caused extensive gastric hemorrhagic lesions which were essentially prevented by nitecapone at doses of 30 mg and higher per kg body weight [10].

Biological context of Nitecapone

• Nitecapone did not influence resting or exercise heart rate, blood pressure, systolic time intervals, or plasma catecholamine levels [11].
• In wild-type mice, the sodium-induced increase in blood pressure was completely normalized by treatment with the COMT inhibitor, nitecapone [12].
• At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018) [13].
• Nitecapone reduces cardiac neutrophil accumulation in clinical open heart surgery [13].
• The inhibition kinetics of rat liver and duodenum soluble catechol-O-methyltransferase (COMT) with a disubstituted catechol OR-462 was studied [14].

Anatomical context of Nitecapone

• RESULTS: Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032) [13].
• METHODS: In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15) [13].
• Inhibition of rat liver and duodenum soluble catechol-O-methyltransferase by a tight-binding inhibitor OR-462 [14].
• Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: modulation by nitecapone, a COMT inhibitor with antioxidant properties [4].
• Now, the action of nitecapone is localized in the hypothalamus since homovanillic acid (HVA) is decreased there, not in the striatum [15].

Associations of Nitecapone with other chemical compounds

• The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity centrally [16].
• PET studies were performed to investigate the effects of a new cathechol-O-methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5-nitrobenzylidene)- 2,4-pentadione]), on the accumulation of dopamine in the striatum and whether it is able to improve [18F]6-fluorodopa imaging of the brain [2].
• Antioxidants, vitamin E and nitecapone, prevented AGE-dependent NF-kappaB activation and normalized PKC activity and associated TGF-beta1 transcription [17].
• The antioxidant properties of nitecapone, a catechol derivative and an inhibitor of catechol-O-methyltransferase, were reported recently [3].
• These results indicate that OR-462 and OR-486 are effective and long-lasting inhibitors of COMT activity [18].

Gene context of Nitecapone

• At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients [13].
• Antioxidant properties of nitecapone (OR-462) [7].
• BACKGROUND: To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients [13].
• Favorable effect of catechol-O-methyltransferase inhibition by OR-462 in experimental models of Parkinson's disease [19].
• Myeloperoxidase activity in myocardial biopsies was higher in the control group (2.3 times higher at 5 minutes and 3.2 times higher at 10 minutes) than in the nitecapone group (p = 0.13) [20].

Analytical, diagnostic and therapeutic context of Nitecapone

• High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone [2].
• Using immobilized metal ion affinity chromatography, we showed that nitecapone binds both copper and iron ions, whereas its affinity for zinc ions is low [6].
• CONCLUSION: Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass [13].
• Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass [13].
• BACKGROUND: Nitecapone has been shown to have a protective effect against ischemia-reperfusion injury in experimental heart transplantation and in Langendorff preparations [20].

References