Tissue distribution, metabolism and effects of bufotenine administered to rats.
Bufotenine (N, N-dimethyl-5-hydroxytryptamine) is a serotonin analog reported to be hallucinogenic. Bufotenine concentrations were measured by liquid chromatography with electrochemical detection after the s.c. injection of bufotenine (1, 30 or 100 mg/kg) into rats. At 1 hr, bufotenine was high in lung, heart and blood and lower in brain and liver. No N-monomethyl-5-hydroxytryptamine was detected, but 5-hydroxyindoleacetic acid (5HIAA) was increased due to bufotenine metabolism. Bufotenine disappeared nearly completely by 8 hr. Bufotenine concentrations were slightly higher in hypothalamus and brain stem than in striatum or cortex; serotonin was slightly decreased, and 5HIAA was increased in these brain regions. Pargyline reduced concentrations of 5HIAA in blood and tissues after bufotenine injection; LY51641 but not deprenyl mimicked pargyline, suggesting type A not type B monoamine oxidase metabolizes bufotenine. Bufotenine injection increased serum corticosterone concentration, an effect not blocked by metergoline at a dose that blocked a similar increase elicited by quipazine. Although only 2% of the serotonin was found in platelet-poor plasma, more than 99% of the bufotenine was found in platelet-poor plasma, indicating that bufotenine is not stored in platelets. These experiments indicate that bufotenine is rapidly eliminated, in part by type A monoamine oxidase, after its injection into rats and that bufotenine penetrates the blood-brain barrier poorly.
Fuller
R W
RW
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Snoddy
H D
HD
Perry
K W
KW
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002027:Bufotenin / Q000378:metabolism* / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003521:Cyclopropanes; D008996:Monoamine Oxidase Inhibitors; D002027:Bufotenin; C000434:Lilly 51641; D006897:Hydroxyindoleacetic Acid