Harman occurs in rat brain, with the highest concentration in the cerebellum and the lowest in the striatum. 2 g/kg ethanol were ineffective with respect to the concentration of harman in the brain whereas 5 g/kg ethanol caused a time-dependent increase in the cerebral cortex as well as the cerebellum. A toxic dose (8 g/kg) of ethanol elicited no change of harman in the brain 3 h following the application. The rise in the harman concentration in the brain did not correlate with the increase of acetaldehyde in the blood after treatment with ethanol suggesting that several mechanisms are involved in the changes of the levels of harman. In subchronic experiments rats were treated with ethanol over a period of 5 or 6 days. Harman increased in the brain whereby the effect seemed to be more pronounced in the cerebellum than in the cerebral cortex. The concentration tended to increase over time and reached control levels again during withdrawal. The time course of the excretion of harman into the urine was similar to that of the brain in that it increased continuously during the period of ethanol treatment and reached control levels again during withdrawal.
Tryptamine was degraded by incubation with rat brain homogenate to an unknown product. The reaction was stimulated by the nonionic detergents Triton X-100 and Lubrol PX and less by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]1-propanesulfonate (CHAPS). The same results were obtained with pig brain and bovine brain. The monoamine oxidase inhibitor pargyline inhibited the reaction strongly, indicating the participation of the enzyme on the reaction. Addition of 17,000 g supernatant from rat brain homogenate increased the formation effectively whereas phospholipids or chloroform/methanol (7:3) extract from the 17,000 g supernatant showed only little or no effect. Chromatographic and electrophoretic properties as well as the chemical reaction of the product with specific reagents suggest that the compound consists of an indole part and an amino acid part. The product could be identified by fast atom bombardment mass spectrometry and by comparison with the synthetic substance (4R)-2-(3-indolylmethyl)-1,3-thiazolidine-4-carboxylic acid. It is formed by the enzymatic oxidation of tryptamine producing indole-3-acetaldehyde which spontaneously cyclizes with free L-cysteine from the tissue. The results suggest that the reaction of biogenic aldehydes with brain macromolecules may proceed via an analogous reaction.
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