PMID: 2484685Jan 1, 1989Paper

Molecular aspects underlying the vasodilator action of molsidomine

Journal of Cardiovascular Pharmacology
E Noack, Martin Feelisch

Abstract

Using different techniques, we measured the kinetics of nitric oxide (NO) liberation from SIN-1, the metabolite of molsidomine, and some related sydnonimines like its thiomorpholinyl analog, compound C 78-0698, and compared it under identical experimental conditions with its biological action at the guanylate cyclase (GC) site, taking this target enzyme as a suitable bioassay. There was a close relationship between half-maximal activation of GC and the velocity of NO release. The thiomorpholinyl analog was slightly more active in NO liberation than SIN-1 and activated the enzyme more rapidly. The kinetics of SIN-1A and SIN-1C formation, determined by high-performance liquid chromatography, could be accurately described by a Bateman equation. Oxyhemoglobin shifted the concentration-response curve of SIN-1 at the isolated soluble GC concentration to the right, whereas methemoglobin was without any effect. The results of our chemical and biochemical studies suggest that velocity and amount of NO formation are the only rate-limiting factors of guanylate cyclase activation by sydnonimines like SIN-1. NO, therefore, exclusively is the mediator of their pharmacodynamic action. In remarkable contrast to nitrate esters like glyceryl tri...Continue Reading

Citations

Jan 1, 1995·British Journal of Pharmacology·L SautebinM Di Rosa
Jun 26, 1998·British Journal of Pharmacology·A AckermannC González
Dec 15, 2006·Nitric Oxide : Biology and Chemistry·Toshinori Suzuki
Apr 29, 2006·Nitric Oxide : Biology and Chemistry·Virginie VinatierPascal Hoffmann
Mar 10, 2006·Nitric Oxide : Biology and Chemistry·Mushfiquddin KhanInderjit Singh
Mar 1, 1992·British Journal of Clinical Pharmacology·H SinzingerP Fitscha
Jan 1, 1992·American Journal of Reproductive Immunology : AJRI·M J TomlinsonI D Cooke
Jun 1, 1995·Annals of Medicine·I Pörsti, I Paakkari

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