The fate of amezinium in humans and animals

The metabolism of 14C-labelled 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, was studied in 6 animal species (dog, cat, rabbit, guinea-pig, rat, and mouse) and in humans. Two-dimensional thin-layer radiochromatography revealed qualitative and quantitative differences between species. In man, dog, cat, guinea-pig, and mouse unchanged amezinium is the principal excretion product, accounting for 56-89% of the radioactivity in the urine whilst metabolites predominate in the rabbit and particularly in the rat. Since besides unchanged amezinium (I) no radioactive substance from the urine is adsorbed on cation exchanger, the first step of biotransformation is assumed to be the formation of uncharged, pharmacologically inactive 5-amino-2-phenyl-3(2H)-pyridazinone (II). The metabolites excreted by man and dog have largely been identified; apart from small quantities of II, hydroxylated pyridazinones and/or their sulfuric acid conjugates were isolated. The formation of the metabolites is discussed.