Chemical synthesis and microvascular effects of new nitric oxide donors in humans

Faisel Khan, Russell J. Pearson, David J. Newton, Jill J. F. Belch, Anthony R. Butler

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Nitric oxide (NO) is produced continuously from the endothelium and plays a pivotal role in the control of vascular tone. Many of the current therapeutic agents that increase blood flow through production of NO have to be taken orally and can produce significant adverse side effects. We now report on some novel NO-donor drugs, based on thiosugars that generate NO spontaneously. From the range of compounds synthesized, D-SNAG (S-nitroso-1-thio-2,3,4,6-tetra-O-acetyl-ß-Dglucopyranose) was as effective a vasodilator as any other and, as it was the easiest to synthesize, we undertook a more detailed evaluation to understand the chemistry and mode of action of its vasodilator effect. From the chemical kinetic data, we found that NO release occurred predominantly by thermal decomposition, with a 20-fold increase in decomposition rate between
    19 and 37 ºC. In the forearm of eight normal male subjects, we found that D-SNAG produced a significant dose-dependent vasodilator effect (P=0.001) with good reproducibility (19 %) on repeated testing. We propose that delivery of NO from D-SNAG to the forearm skin microvessels most probably occurs by diffusion across the epidermis. Since such compounds release NO in a
    non-enzymic manner following topical application, they might produce an attractive therapeutic source of localized NO delivery without inducing systemic side effects.
    Original languageEnglish
    Pages (from-to)577-584
    Number of pages8
    JournalClinical Science
    Volume105
    Issue number5
    DOIs
    Publication statusPublished - Nov 2003

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    Nitric Oxide Donors
    Nitric Oxide
    Vasodilator Agents
    Forearm
    Thiosugars
    Microvessels
    Epidermis
    Endothelium
    Blood Vessels
    Hot Temperature
    Skin
    Therapeutics
    Pharmaceutical Preparations

    Cite this

    Khan, Faisel ; Pearson, Russell J. ; Newton, David J. ; Belch, Jill J. F. ; Butler, Anthony R. / Chemical synthesis and microvascular effects of new nitric oxide donors in humans. In: Clinical Science. 2003 ; Vol. 105, No. 5. pp. 577-584.
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    Chemical synthesis and microvascular effects of new nitric oxide donors in humans. / Khan, Faisel; Pearson, Russell J.; Newton, David J.; Belch, Jill J. F.; Butler, Anthony R.

    In: Clinical Science, Vol. 105, No. 5, 11.2003, p. 577-584.

    Research output: Contribution to journalArticle

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