title: NO donors. Part 18: Bioactive metabolites of GTN and PETN--synthesis and vasorelaxant properties.
abstract: The vasodilators glyceryl trinitrate (GTN) and pentaerythrityl tetranitrate (PETN) are supposed to be degraded in vivo to the lower nitrates PETriN, PEDN, PEMN, 1,2-GDN, 1,3-GDN, 1-GMN, and 2-GMN. We synthesized these bioactive metabolites as reference compounds for pharmacokinetic studies. The use of HPLC-methods for monitoring the stepwise reduction of PETN to lower nitrates and the syntheses of the glyceryl dinitrates proved advantageous. Furthermore, we measured the vasorelaxant properties of all metabolites by performing organ bath experiments with porcine pulmonary arteries. In general, the vasodilator potency increases with the number of nitrate moieties in the compound.
authors.affiliation: Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Jena, Thuringia, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Lange
authors.forename: Andreas
authors.initials: A
authors.lastname: Koenig
authors.forename: Carolin
authors.initials: C
authors.lastname: Roegler
authors.forename: Andreas
authors.initials: A
authors.lastname: Seeling
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D004897:Erythrityl Tetranitrate / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D005996:Nitroglycerin / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D004897:Erythrityl Tetranitrate; D005996:Nitroglycerin