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

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Amidines
Nitric Oxide Synthase
Arginine
Protein Isoforms
Nitric Oxide Synthase Type III
Nitric Oxide Synthase Type II
Citrulline
Nitroarginine
Nitrites
Endothelial Cells
Macrophages

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Amidines are potent inhibitors of nitric oxide synthases : preferential inhibition of the inducible isoform. / Southan, Garry J.; Szabo, Csaba; O'Connor, Michael P.; Salzman, Andrew L.; Thiemermann, Christoph.

In: European Journal of Pharmacology: Molecular Pharmacology, Vol. 291, No. 3, 30.11.1995, p. 311-318.

Research output: Contribution to journalArticle

Southan, Garry J. ; Szabo, Csaba ; O'Connor, Michael P. ; Salzman, Andrew L. ; Thiemermann, Christoph. / Amidines are potent inhibitors of nitric oxide synthases : preferential inhibition of the inducible isoform. In: European Journal of Pharmacology: Molecular Pharmacology. 1995 ; Vol. 291, No. 3. pp. 311-318.
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