alpha-Methylated tryptamine derivatives induce a 5-HT receptor-mediated head-twitch response in mice.
The two alpha-methylated tryptamine derivatives, 5- (5-FMT) and 6-fluoro-alpha-methyltryptamine (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-HT2 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.
Tadano
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Neda
M
M
Hozumi
M
M
Yonezawa
A
A
Arai
Y
Y
Fujita
T
T
Kinemuchi
H
H
Kisara
K
K
D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006257:Head; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D051379:Mice; D016548:Prosencephalon / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D013997:Time Factors; D014363:Tryptamines / Q000494:pharmacology*
D011985:Receptors, Serotonin; D014363:Tryptamines; D005473:Fluoxetine; D003533:Cyproheptadine; C030820:tryptamine