DISTRIBUTION, METABOLISM AND EXCRETION OF BUFOTENINE IN THE RAT WITH PRELIMINARY STUDIES OF ITS O-METHYL DERIVATIVE

¹ Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

Studies of the biologic fate of bufoatenine and O-methyl-bufo-tenine in the rat are presented. The syntheses of these compounds labeled with C¹⁴ and methods for estimation of unchanged compounds and metabolites of bufotenine in biologic material are described. After i.v. administration, the concentration of bufotenine in brain remained very low at all times. O-methyl-bufotenine, which is more lipid-soluble, quickly reached a brain-blood ratio 15 times higher than that of bufotenine. The biologic half-life of bufotenine in blood was 40 min. The metabolites in liver, lung and heart were so concentrated relative to unchanged drug that metabolism was probably occurring in these tissues. About 91% of the dose of bufotenine was excreted in the 72-hr urine, most of it in 12 hr. Less than 2% was eliminated in the feces. About 6% was unchanged bufotenine, 15% was 5-hydroxyindole acetic acid and 35% was the glucuronide conjugate of bufotenine. Bufotenine is somewhat unstable in ether extracts stored at 5°C; 5-hydroxyindole acetic acid is puite unstable under these conditions even more unstable in aqueous acid solutions equilibrated with ether.