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Journal of Pharmacology And Experimental Therapeutics, Vol. 173, Issue 1, 26-30, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

BLOOD LEVELS AND URINARY EXCRETION OF HARMINE AND ITS METABOLITES IN MAN AND RATS

THEODORE A. SLOTKIN 1, VICTOR DiSTEFANO 1, and WILLIAM Y. W. AU 1

1 Department of Pharmacokgy, University of Rochester, Rochester, New York

This study quantifies blood and urinary levels of harmine and its urinary metabolites (harmol, harmol glucuronide and harmol sulfate) in man and rats after the i. v. administration of 0.5 mg of harmine per kg (man and rats) and 5 mg of harmine per kg (rats). Metabolites were analyzed by paper chromatography, enzymatic hydrolysis and fluorometry. Within two minutes after administration, 10% of the dose was found in the blood of either species; after four hours, le1%. Both species excreted the same urinary metabolites. After 48 hours, total urinary excretion was about the same, although the excretion rate was higher in man. Urinary harmine and harmol concentrations were insignificant. Harmol sulfate was the primary conjugate in rats; harmol glucuronide excretion predominated in man. The ratio of the rate of harmol glucuronide excretion to the rate of harinol sulfate excretion (G/S) increased with time in rats given 5 mg of harmine per kg, but was relatively constant in rats and humans given 0.5 mg of harmine per kg. Administration of Na2SO3 to rats given 5 mg of harmine per kg prevented this rise in G/S, suggesting that 3'-phosphoadenosine 5'-phosphosulfate plays a limiting role in the formation of harmol sulfate.

Submitted on July 3, 1969
Accepted on January 5, 1970




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