Abstract
Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H(2)O(2). These compounds also displayed vasodilatory activity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arginine / metabolism
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Dioxanes / chemistry*
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Dioxanes / pharmacology*
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Drug Design
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Drug Evaluation, Preclinical / methods
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Guanidine / chemistry*
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Guanidines / chemistry*
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Guanidines / pharmacology*
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Guinea Pigs
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Horseradish Peroxidase / metabolism
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Hydrogen Peroxide / chemistry
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Hydrogen Peroxide / metabolism
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In Vitro Techniques
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Mesenteric Arteries / drug effects
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Mesenteric Arteries / physiology
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Nitric Oxide Donors / chemistry*
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Nitric Oxide Donors / metabolism
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Nitric Oxide Donors / pharmacology*
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Nitric Oxide Synthase / metabolism*
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Nitrites / metabolism
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Structure-Activity Relationship
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Vasodilator Agents / chemistry
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Vasodilator Agents / metabolism
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Vasodilator Agents / pharmacology
Substances
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Dioxanes
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Guanidines
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N-hydroxyguanoxan
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Nitric Oxide Donors
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Nitrites
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Vasodilator Agents
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Arginine
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Hydrogen Peroxide
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Horseradish Peroxidase
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Nitric Oxide Synthase
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Guanidine