Abstract
The two alpha-methylated tryptamine derivatives, 5- (5-FMT) and 6-fluoro-alpha-methyl- tryptamine (6-FMT), rapidly induced a head-twitch response (HTR) in mice. Two derivatives that lack the methyl group in their chemical structures, 5- (5-FT) and 6-fluorotryptamine (6-FT), did not induce the HTR. The induced HTR was depressed by pretreatment with cycloheptadine, p-chlorophenylalanine or fluoxetine, but was potentiated by 5,7-dihydroxytryptamine. Both 5- and 6-FMT increased brain 5-HT levels in hypothalamus, hippocampus, brainstem, striatum and cortex. 5-FMT decreased the levels of 5-hydroxyindoleacetic acid in those regions, but 6-FMT caused a significant decrease in only the hypothalamus and cortex. The two methylated derivatives inhibited mouse brain MAO-A activity more selectively than non-methylated derivatives. The results suggest that the HTR induced by 5- and 6-FMT may result from increased activity of central 5-HT neurons, probably due to increased 5-HT levels after MAO-A inhibition. This probably results in release of 5-HT with a concomitant increased interaction with postsynaptic 5-HT 2 receptors. The present results also indicate the importance of the methyl group to selective MAO-A inhibition by the substrate-analogues tested, and the concomitantly induced animal behavior.
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