Abstract:
Glyceryl trinitrate (GTN) is classified as an organic nitrate vasodilatordrug. GTN is considered to be a prodrug because it undergoes biotransformationat its site of action to form nitric oxide (NO) or a NO adduct, which producesits pharmacologic effect. The objectives of this study were to determinewhether the hippocampus can biotransform GTN to NO using aerobic conditions,and whether biotransformation of GTN to NO is age-dependent during postnatallife. Time-dependent formation of NO occurred during the incubation of 100<emph type="8">µM GTN with 2.5% (w/v) homogenate ofguinea-pig hippocampus at 37°C using aerobic conditions. GTN-derivedNO formation was similar in magnitude for the three selected postnatal agesthat were studied, that is, postnatal days 10, 20 and > 60. The datademonstrate that the capacity of the hippocampus for NO formation from GTN isfully developed in the guinea-pig in early postnatal life. In view of thesefindings, it is conceivable that a NO donor drug, selectively metabolized toNO in the hippocampus, could be a useful therapeutic intervention to mitigatestructural and/or functional defects in this brain region resulting fromdecreased NO formation or availability.