QUINDONIUM AND ITS GLUCURONIDE: TISSUE DISTRIBUTION IN NORMAL AND STRESSED MICE AND METABOLIC INTERACTIONS INVOLVING BIOGENIC AMINES AND GLYCOGEN

¹ Biochemistry Department, Warner-Lambert Research Institute, Morris Plains, New Jersey

Biochemical aspects of the pharmacologic activity of the cardiovascular agent, quindonium, as well as the distribution of the compound and its glucuronide in tissues of the mouse have been examined. The effect of quindonium on intestinal motility could not be related to release of serotonin (in mice), and the positive inotropic effect on the heart could not be related either to the release of norepinephrine (in guinea pigs) or to the activation of glycogenolysis (in rats). Although quindonium potentiates the inotropic effect of isoproterenol, it did not interact with isoproterenol relative to glycogenolysis in the heart of rats. When Ketodase was used to hydrolyze its glucuronide and a fluorometric assay was used for free quindonium, high levels of quindonium glucuronide were found in tissues minutes after the drug was injected and for hours afterward. The imposition of hemorrhagic stress, with restraint, and of a lethal dose of depot epinephrine caused higher concentrations of free quindonium to be present in tissues, an effect which has been interpreted as possibly due to lysosomal damage with the consequent liberation of -glucuronidase.