Amidines are potent inhibitors of nitric oxide synthases: preferential inhibition of the inducible isoform

Garry J. Southan, Csaba Szabó, Michael P. O'Connor, Andrew L. Salzman, Christoph Thiemermann

    Research output: Contribution to journalArticle

    44 Scopus citations

    Abstract

    We evaluated the ability of simple alkyl amidines to inhibit the activity of the inducible isoform of nitric oxide (NO) synthase in vitro. In immunostimulated J774 macrophages, 2-iminopiperidine (EC50 = 10 μM) and butyramidine (EC50 = 60 μM) were more potent than NG-methyl-L-arginine (EC50 = 70 μM) in inhibiting nitrite formation. The five amidines tested for their ability to inhibit the conversion of L-arginine to L-citrulline by bovine endothelial cell homogenates (a source of the constitutive, endothelial NO synthase isoform) were less effective than NG-nitro-L-arginine or NG-methyl-L-arginine. The rank-order of the potencies of the amidines against the en endothelial NO synthase was, in general, similar to the rank-order of the pressor effects of these agents in anesthetized rats. Thus, certain amidines are potent inhibitors of NO synthase, and are more selective towards the inducible NO synthase than the commonly used L-arginine based NO synthase inhibitors.

    Original languageEnglish (US)
    Pages (from-to)311-318
    Number of pages8
    JournalEuropean Journal of Pharmacology: Molecular Pharmacology
    Volume291
    Issue number3
    DOIs
    StatePublished - Nov 30 1995

    Keywords

    • Amidine
    • Blood pressure
    • Butyramidine
    • Endothelium
    • Endotoxin
    • Inflammation
    • Isothiourea
    • Nitric oxide, NO
    • Shock

    ASJC Scopus subject areas

    • Pharmacology

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