Occurrence and partition of the beta-carboline norharman in rat organs.
The beta-carboline norharman was determined in plasma, brain, liver, kidney, spleen, heart and lung of the rat using HPLC with fluorescence detection. In order to improve the speed and sensitivity of this assay an earlier published sample clean-up extraction procedure and HPLC method were adjusted. Norharman was found to be present in plasma as well as in all organs tested, concentrations in organs being about 80 times higher than those in plasma. Intraperitoneal injections of 2 and 100 mg/kg norharman showed that the partition of norharman between organs and plasma is about 3. Only the highest dose was found to have behavioural effects, viz. alerting reactions, a decrease in motor and exploratory activity, sedation, loss of righting reflex and after 30 min complete muscle relaxation, but no catatonia was observed. Norharman was found to be metabolized by the liver with a half live of about 20 min, whereas all other organs tested did not show any norharman clearing capacity. The results suggest that norharman is not likely the cause of psychosis, but a natural sedative and by- or coproduct of a more primary biochemical derangement.
Section Pathophysiology of Behaviour, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002243:Carbolines; D002851:Chromatography, High Pressure Liquid; D006247:Harmine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D002243:Carbolines; D006247:Harmine; C010262:norharman