Circulating and brain metabolites of minaprine in the baboon

A mixture of 15N-labelled, 14C-labelled and unlabelled minaprine was administered orally to three baboons, and metabolites in blood, urine and brain investigated. Biological samples were extracted with dichloromethane and the radioactive components extracted were analysed by t.l.c. and autoradiography. Compounds identified by comparing their physiochemical properties with those of synthetic standards and by g.l.c.-mass spectrometry were minaprine, 3-[2-(3-oxo)morpholino-ethylamino]-4-methyl-6-phenylpyridazine, 3-amino-4-methyl-6-phenylpyridazine, 3-[2-(aminoethyl)ethylamino]-4-methyl-6-phenylpyridazine, p-hydroxyminaprine and minaprine N-oxide. In addition to the urinary metabolites, two circulating metabolites were detected: metabolite A, 3-[2-(3-oxo)morpholino-ethylamino]-4-methyl-6-phenylpyridazine, and metabolite B (unidentified). All circulating metabolites appeared very early in blood, confirming the rapid and extensive metabolism of the drug. Metabolites A, B and 3 (p-hydroxyminaprine) were the major metabolites present in plasma. The parent drug was not the major circulating form, and was present in a higher concentration in erythrocytes than in plasma. Erythrocytes might act as a reservoir of the drug and could explain the relatively slow blood clearance of minaprine despite its rapid metabolism. The qualitative metabolic profile in brain tissue was similar to that in blood.