PHARMACOLOGICAL COMPARISON OF THE STEREOISOMERS OF GLYCERYL-1-NITRATE

The enantiomers of glyceryl-1-nitrate, a metabolite of glyceryl trinit rate, were pharmacologically characterized in vitro and in animals. In the Langendorff heart (l) G-1-N was double as potent as (d) G-1-N wit h respect to the enhancement of coronary flow. The two enantiomers sho wed almost the same dose-response curves in rabbit aortic strips contr acted with phenylephrine. In the same model there were no enantiospeci fic differences in the development of cross-tolerance to glyceryl-trin itrate. In anaesthetized rabbits, intravenous (l) G-1-N reduced the bl ood pressure slightly more than (d) G-1-N, while in the conscious dog the blood pressure lowering effect of (d) G-1-N was greater and had a much longer duration (4-6 versus 2 h) than that of (l) G-1-N. The diff erences in dogs are probably explained by enantiospecific pharmacokine tics: (d)G-1-N had higher plasma levels and showed a longer half-life of elimination than (l) G-1-N (more than 5 h versus 2.7 h). Both enant iomers enhanced the rate of survival after acute coronary ligature in rats with a tendency to higher long-term survival rates after the (d) form.