Urinary metabolites of harmine in the rat and their inhibition of monoamine oxidase

Abstract

Tritiated harmine hydrochloride (5 mg/kg, i.p.) was given to male rats daily for 3 days and urine was pooled. Gel filtration on Sephadex G-15 yielded 5 radioactive fractions, I–V. Fraction V was shown to be harmol by comparison with authentic harmol by gel filtration, fluorescence spectrophotometry, paper chromatography, and paper electrophoresis. Fraction IV was shown similarly to be harmine. Pre-injecting rats with 35S-Na 2SO 3 yielded a radioactive fraction corresponding to III; hydrolysis of III by aryl sulfatase yielded harmol; III was therefore identified as harmol sulfate. Hydrolysis of II by β-glucuronidase yielded harmol and glucuronic acid; II was therefore identified as harmol glucuronide. Fraction I was shown to be a radioactive impurity in the injection solution. The urinary metabolites occurred in the percentages: V–11 per cent, IV-2 per cent, III-69 per cent, II-18 per cent. Rat liver mitochondrial monoamine oxidase activity, measured by the conversion of benzylamine to benzaldehyde, was inhibited 27 per cent at 10 −5M, V; 85 percent at 10 −6M, IV; 29 per cent at 10 −5M, III; and 52 per cent at 10 −6M, II.