Nitroglycerin metabolism

Servent D, C Ducrorq, Y Henry, A Guissani, M Lenfant (1991) Nitroglycerin metabolism by Phanerochaete chrysosporium evidence for nitric oxide and nitrite formation. Biochim Biophys Acta 1074 320-325. 

Lau, D. T. W., Benet, L. Z., Nitroglycerin metabolism in subcellular fractions of rabbit liver. Dose dependency of glyceryl dinitrate formation and possible involvement of multiple isoenzymes of glutathione S-transferases. Drug Metab. Dispos. 18 (1990), p. 292-297... 

R., Peterson, T. E., Harrison, D. G., Nitroglycerin metabolism in vascular tissue role of glutathione transferases and relationship between NO and N02 formation. Biochem. J. 292... 

Identification of the subcellular site for nitroglycerin metabolism to nitric oxide in bovine coronary smooth muscle cells. J. Pharmacol. Exp. Ther. 253 (1990), p. 614-619... 

D. T. W. Lau, L. Z. Benet, Nitroglycerin Metabolism in Subcellular Fractions of Rabbit Liver. Dose Dependency of Glyceryl Dinitrate Formation and Possible Involvement of Multiple Isozymes of Glutathione S-Transferases , Drug Metab. Dispos. 1990, 18, 292 - 297. 

Several other issues also add to the controversy concerning the involvement of CYP in nitroglycerin metabolism and vasodilation. Although McDonald and Bennett (1993) showed that vascular CYP are present in the rat aorta, it is not certain that the enzymes exist in sufficient quantities in vivo to metabolize nitroglycerin. In their experiments 100 aortas were required to... 

Isosorbide is rapidly absorbed and undergoes rapid first-pass metaboHsm by the Hver. The bioavaUabUity of the subHngual and chewable tablets is 59% and 22%, respectively, for the regular tablet. Isosorbide is metabolized to isosorbide-2-mononitrate and isosorbide-5-mononitrate, both of which have pharmacologic activity. The elimination half-Hves of subHngual and po isosorbide dinitrate ate 1 and 4 h, respectively. Those of the 2- and 5-mononitrate metaboHtes are 1.5—3.1 h and 4—5.6 h, respectively. The two metaboHtes prolong the elimination half-life of the dinitrate. Adverse effects with isosorbide are similar to those described for nitroglycerin (99). 

NO is recognized as a mediator of bone cell metabolism, where it regulates osteoblast and osteoclast activity [141-143]. Osteoporosis, which frequently occurs in postmenopausal women, is a systemic skeletal disease associated with abnormal bone resorption. Addition of NO or NO donors to osteoclasts in vitro results in a reduction in bone resorption, whereas NO synthase inhibitors increase bone resorption, both in vitro and in vivo. Further research has shown that NO reduces bone resorption, via inhibition of the cysteine protease cathepsin K, which is believed to be a key protease in bone resorption. Most of the NO donors, i.e., nitroglycerin, 3-... 

Metabolism of nitroglycerin by smooth muscle cells. Involvement of glutathione and glutathione S-transferase. Biochem. Pharmcol. 43... 

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