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Bradley PB, Briggs I. 
“Further Studies On The Mode Of Action Of Psychotomimetic Drugs: Antagonisms of The Excitatory Actions Of 5-hydroxytryptamine By Methylated Derivatives of Tryptamine”. 
Br. J. Pharmac.. 1974;50:345-354.
Abstract
I The actions of 5-methoxytryptamine (5-MeOT), N,N-dimethyltryptamine (DMT), 5 - hydroxy-N,N-dimethyltryptamine (bufotenine, 5-HODMT) and 5-methoxy-NN - dimethyltryptamine (5-MeODMT),- and their interactions with 5-hydroxytryptamine (5 - HT), acetylcholine, (-)-noradlenaline, and glutamate were studied by microiontophoresis on single neurones in the brain stem of rats anaesthetized with urethane or decerebrate cats. 2 Like D-lyser'gic acid diethylamide (LSD 25) the three psychotomimetic derivatives (DMT, 5-HODMT, 5-MeODMT) specifically antagonized 5-HT excitations of single neurones, but the non-psychotomimetic 5-MeOT had no antagonistic effects. 3 In contrast to LSD 25, the psychotomimetic tryptamines only rarely antagonized glutamate effects, indicating that tine' excitatory 5-HT receptors and the glutamate receptors on the-same neurones may be closely related spatially, but are separate. 4 The methylated tryptamine derivatives were able to mimic the actions of 5-HT on neurones. The non-psychotomimetic' 5-MeOT was most potent in this respect, while the other three derivatives which are psychotomimetic, were less active. 5 The 5-HT mimicking actions of 5-MeOT were the same in rats pretreated with p - chlorophenylalanine or reserpine as in untreated rats. It therefore seems that the 5-HT actions are unlikely to be due to release of 5-HT, but are due to direct actions on 5-HT receptors. 6 The evidence presented supports the hypothesis that LSD-like psychotomimetics act by an antagonism of 5-HT in the lower brain stem, and is not compatible with the suggestion that the psychotomimetic action of these drugs is related to 5-HT receptor stimulation.
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