Nitroarginine

Most NOS inhibitors are stmcturaHy related to L-arginine and do not differentiate between the isoforms (Table 15). t - / 7-Methy1 arginine (l-NMA) (264) is a competitive inhibitor and also irreversibly inhibits NOS. T.-/ 7-Nitroarginine (l-NNA) (265), L-AP -nitroarginine methyl ester (t.-NAMF) (266),... 

DMSO Dimethyl sulfoxide DNA Deoxyribonucleic acid d-NAME D-Nitroarginine methyl... 

NADPH Reduced nicotinamide adenine dinucleotide phosphate NAF Neutrophil activating factor l-NAME L-Nitroarginine methyl ester... 

M Bergmann, L Zervas, H Rinke. New process for the synthesis of arginine peptides, (nitroarginine). Hoppe-Seyler s Z Physiol Chem 224, 40, 1932. 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

Gibson, A., Mirzazadeh, S., Hoffs, A. J., and Moore, P. K. (1990). L-N -Monomethylar ginine and L-N -nitroarginine inhibit non-adrenergic, noncholinergic relaxation of the mouse anococcygeus muscle. Br. ]. Pharmacol. 99, 602-606. 

L-nitroarginine <28> (<28> 5fold higher concentration than L-Arg, 28% inhibition [35]) [35]... 

Several synthetic methods for the reduction of a-amino esters have also been reported. The reduction of methyl or ethyl esters by diisobutylaluminum hydride (DIBAL-H) at low temperature (—78 °C) has been described as useful for the preparation of a-amino aldehydes. 1118 20 Again, this method suffers from overreduction. Reductive methods involving mild reductive agents have been described. The reduction of phenyl esters 6 21 (readily prepared from the corresponding amino acid 5) with lithium tri-ferf-butoxyaluminum hydride is efficient for the preparation of various Boc-a-amino aldehydes including Na-Boc-7V J-nitroargininal and A7a-Boc-W"-Z-argininal (Scheme 5). 

Scheme 4 Synthesis of an A -Nitroargininal Hemiaminal Ether Hydrochloride 361...

Sawyer, T.W. (1998a). Characterization of the protective effects of L-nitroarginine methyl ester (L-NAME) against the toxicity of sulphur mustard in vitro. Toxicology 131 21-32. 

Huang H, Martasek P, Roman LJ, Masters BS, Silverman RB. f2-nitroarginine-containing dipeptide amides. Potent and highly selective inhibitors of neuronal nitric oxide synthase. J. Med. 

As might be anticipated from the dependency of CBF on intracellular cAMP, -agonists elevate CBF, although the concentrations required to do this are greater than those required for bronchodilatation (Pavia etal., 1984). Evidence from primary cultures of bovine bronchial epithelium has been presented which su ests that a component of the isoprenaline-stimulated increase in CBF is dependent up)on the formation of nitric oxide (NO Jain eteU., 1993). The nitric oxide synthase (NOS) inhibitors L-nitromonomethyl arginine (L-NMMA) and L-nitroarginine methyl ester (L-NAME) both reduced... 

L-NAME (L-A/ -nitro-L-arginine methyl ester Af -nitro-t-arglnine methyl ester nitroarginine methyl ester) is a NITRIC OXIDE SYNTHASE INHIBITOR, extensively used as a pharmacological tool. l>NI 7-nitroindazole. 

L NNA (i-Af -aminoarglnine) is a nitric oxide synthase INHIBITOR, extensively used as a pharmacological tool. l-NOAG (i-Af -nitroarginine) is a nitric oxide synthase inhibitor, extensively used as a pharmacological tool. 

L-AP>nitroarginine methyl ester l-NAME. iV -nitro-L-arginine methyl ester l-NAME. nitrofural nitrofiirazone. nitrofurantoin (ban. inn] (Furadantln " Macrobid ... 

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