620-12-2Relevant articles and documents
NO donors. Part 18: Bioactive metabolites of GTN and PETN-Synthesis and vasorelaxant properties
Lange, Kathrin,Koenig, Andreas,Roegler, Carolin,Seeling, Andreas,Lehmann, Jochen
experimental part, p. 3141 - 3144 (2010/01/17)
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.
STUDY OF NITRATION EQUILIBRIUM IN THE GLYCERIN-AQUEOUS NITRIC ACID SYSTEM. 1. DEPENDENCE OF THE EQUILIBRIUM CONSTANTS OF NITRATION REACTIONS ON THE TEMPERATURE, ACIDITY OF THE MEDIUM, AND STRUCTURE OF THE NITRATED COMPOUND
Kazakov, A. I.,Lagodzinskaya, G. V.,Andrienko, L. P.,Yunda, N. G.,Korolev, A. M.,et al.
, p. 1560 - 1565 (2007/10/02)
The equilibrium constants of seven sequential-parallel reactions of conversion of glycerin into glycerin trinitrate in aqueous HNO3 were measured.The effect of the acidity of the medium on the equilibrium nitration constants is correlated with processes of protonation of glycerin and its nitrates.The equilibrium nitration constants are higher for primary hydroxides than for secondary hydroxides, and they decrease in both series in going from glycerin to its dinitrates.
The pattern of glyceryl nitrates after oral administration of glyceryl trinitrate.
Laufen,Leitold
, p. 103 - 105 (2007/10/02)
An oral dose of 20 mg sustained release glyceryl trinitrate (GTN, Nitro Mack Retard) was administered to 6 healthy human subjects. In the plasma of all subjects the metabolically generated glyceryl nitrates glyceryl 1,2-dinitrate (G-1,2-DN), glyceryl 1,3-dinitrate (G-1,3-DN), glyceryl 2-nitrate (G-2-N) and glyceryl (G-1-N) could be identified, but no intact GTN was found. The nitrate metabolites showed sustained plasma profiles which can be explained by a slow release of GTN with subsequent complete first-pass denitration. The plasma concentrations of the mononitrates were generally higher than those of the dinitrates. G-1,2-DN and G-2-N, the metabolites which contain a nitrate group in the central position, showed higher concentrations than the respective isomeric compounds. The combined glyceryl dinitrates reached concentrations between 10.2 and 21.7 ng/ml, the combined mononitrates varied from 70.4 to 106.8 ng/ml. The ratios of the areas under the curve G-1,3-DN:G-1,2-DN:G-1-N:G-2-N were 1:4:19:64, on average. Taking into consideration the relative vasodilator potencies of glyceryl nitrates in the animal, our results give rise to the hypothesis that the glyceryl dinitrate metabolites participate in the clinical efficacy of large oral doses of sustained release GTN.
