Occurrence and partition of the beta-carboline norharman in rat organs.
D Fekkes, W T Bode
Life Sciences 1993 DOI: 10.1016/0024-3205(93)90689-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal pharmacokinetic and behavioral study Peer reviewed |
|---|---|
| Population | Rats (Wistar), male |
| Intervention | Norharman |
| Dose | 2 and 100 mg/kg |
| Keywords | Myocardium Liver Lung Kidney Brain Spleen Animals Rats, wistar Harmine Carbolines Behavior, animal Tissue distribution Time factors Male |
| Key points | Norharman was present in rat plasma and all organs tested, at organ concentrations about 80 times plasma levels. Only the 100 mg/kg intraperitoneal dose produced behavioral effects (alerting, reduced motor and exploratory activity, sedation, loss of righting reflex, muscle relaxation without catatonia). The liver cleared norharman with a half-life of about 20 minutes, while other organs showed no clearing capacity. The authors suggest norharman is unlikely to cause psychosis and may act as a natural sedative and by- or coproduct of a more primary biochemical derangement. |
Abstract
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.