title: N-Methyl-2-pyridone-5-carboxamide is 1-methylnicotinamide metabolite of low cyclooxygenase-dependent vasodilating activity.
abstract: 1-Methylnicotinamide (MNA) is a primary metabolite of nicotinamide recently proven to cause systemic increase in PGI(2) plasma levels in an unknown mechanism. Our present study was aimed at verifying whether the increased production of PGI(2), a vasodilating prostanoid, in response to MNA, its metabolite N-methyl-2-pyridone-5-carboxamide (Met2PY), and nicotinamide may be reproduced under in vitro conditions. Since prostacyclin is a vasodilating prostanoid, we also performed the functional tests in the ex vivo model of coronary vascular bed perfusion to evaluate the vasoactive properties of those compounds. We did not observe any significant effect of the tested drugs on either PGI(2) or PGE(2) secretion in our in vitro model. Nicotinamide at the concentrations of 10 and 100 μmol/l and 100 μmol/l Met2PY slightly but significantly increased coronary flow in rat heart. These increases, however, remained very low when compared to that induced by the reference compound, bradykinin (100 nmol/l). Perfusion of rat hearts with Met2PY in the presence of 50 μmol/l indomethacin resulted in decreased coronary flow, which proves that the effect is cyclooxygenase dependent. We conclude that MNA metabolites should be more carefully addressed in reference to pro-prostacyclin activity and that systemic mechanism of MNA-induced PGI(2) production needs further clarification.
authors.affiliation: Chair of Laboratory Diagnostics, Department of Haemostasis and Haemostatic Disorders, University Clinical Hospital No 2, Medical University of Lodz, Lodz, Poland. tomasz.przygodzki@umed.lodz.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Przygodzki
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Grobelski
authors.forename: Piotr
authors.initials: P
authors.lastname: Kazmierczak
authors.forename: Cezary
authors.initials: C
authors.lastname: Watala
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009536:Niacinamide; C005211:N'-methyl-2-pyridone-5-carboxamide; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin; C024058:N(1)-methylnicotinamide; D007213:Indomethacin