A -nitro-L-arginine methyl ester

A -Nitro-L-arginine methyl ester (L-NAME) NOS inhibition Less selective NOS inhibitor... 

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-NAME (N-nitro-L-arginine methyl ester), like L-NMMA, is a structural analogue of L-arginine and competes with L-arginine for NO-synthase, which uses L-arginine as a substrate for the formation of NO. L-NMMA and L-NAME are very effective NO-synthesis inhibitors, both in vitro and in vivo. 

N-Nitro-L-arginine methyl ester (L-NAME) is an inhibitor of NOS L-NAME reportedly reduces the volume of cortical and striatal infarct after middle cerebral artery occlusion in the rat. This protection can be reversed by co-injection of L-arginine. L-NAME also reduced the excitotoxic damage induced by NMDA injection. Finally, the authors showed that L-NAME reduced glutamate efflux produced by ischaemic injury in rats. The authors concluded that NOS induced by NMDA receptor overstimulation is a key event in the neuronal injury cascade (Buisson eta/., 1993). 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

S. Gumuslu, M. Serteser, T. Ozben, S. Balkan, and E. Balkan, Inhibitory Role of N -nitro-L-Arginine Methyl Ester (L-NAME), a Potent Nitric Oxide Synthase Inhibitor on Brain Malondialdehyde and Conjugated Diene Levels During Focal Cerebral Ischemia in Rats. Clinica ChimicaActa 267(2) (1997) 213-223. 

Vargas F, Osuna A, Fernandez-Rivas A Vascular reactivity and flow-pressure curve in isolated kidneys from rats with N-nitro-L-arginine methyl ester-induced hypertension. J Hypertens 14 373-9,1996... 

Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester Adams, Michael L. Kalicki, Joelle M. Meyer, Edward R. Cicero,... 

Wink et al. (1993b) demonstrated that NO (and/or reactive species formed from -NO autoxidation) inhibits CYP activity in both reversible and irreversible manners. Khatsenko et al. (1993) reported that the decrease in total microsomal CYP caused by endotoxin injection in rats is inhibited by coadministration of N°-nitro-L-arginine methyl ester (l-NAME), an inhibitor of NO synthase (NOS), indicating that the decrease in drug-metabolizing activity under inflammatory conditions is a result of endogenous -NO synthesis. Stadler etal. (1994) demonstrated a decrease in CYP activity and protein expression in vitro in isolated hepatocytes as a result of -NO synthesis. 

Other studies have discounted a prejunctional effect of NO on NE release from sympathetic nerve endings. In this context neither NO, supplied as acidified nitrite to the transmurally stimulated guinea pig pulmonary artery (Cederqvist and Gustafsson, 1994) or endogenously released by acetylcholine in the mesenteric artery of the dog (Toda et al., 1990), nor the prevention of NO synthesis with NNA and N -nitro-L-arginine methyl ester in the rabbit pulmonary artery (Schinozuka et al., 1992) and the rat tail artery (Thorin and Atkinson, 1994), nor its destruction with hemoglobin in the coronary vessels of the isolated rabbit heart (Wennmalm et al., 1989) were found to affect NE release. 

Bagetia, G., lannanone, M., Scorsa. A. M., and Ni.stico. G. (1992). Tacrine-Induced seizure.s and brtun damage in LiCl-trcated rats can be prevented by N-nitro-L-arginine methyl ester, tar. I Pharmacol. 213, 301-304. 

Administration of an aqueous extract of yohimbe at doses of 1 to 1000 ng/kg elicited a dose-dependent increase in mean blood pressure and an increase in medullary blood flow. Both the pressor action and renal medullary vasodilation were blocked by endothelin A and B receptor antagonists in combination. N -nitro-L-arginine methyl ester also inhibited the increase in medullary blood flow induced by yohimbe. The authors of the study concluded that preliminary observations indicate that, in addition to the a-adrenergic antagonist actions that characterize yohimbine, yohimbe possesses endothelin-like actions and affects nitric oxide production in the renal circulation (Ajayi et al. 2003). 

Capasso, R, N. Mascolo, A.A. Izzo, and T.S. GagineUa. 1994. Dissociation of castor oil-induced diarrhoea and intestinal mucosal injury in rat Effect of N -nitro-L-arginine methyl ester. Br. /. Pharmacol. 113(4) 1127. 

For quantification of basal vascular nitric oxide ( NO) production from isolated vessels, Kleschyov et al. (2000) incubated rabbit aortic or venous strips with 250 (iM colloid Fe/diethyldithiocarbamate, which resulted in a linear increase in tissue-associated NO-Fe/diethyldithiocarbamate electron paramagnetic resonance signal during 1 h. Removal of endothelium or addition of 3 mM N -nitro-L-arginine methyl ester inhibited the signal. 

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