FURTHER STUDIES ON THE MODE OF ACTION OF PSYCHOTOMIMETIC DRUGS: ANTAGONISM OF THE EXCITATORY ACTIONS OF 5‐HYDROXYTRYPTAMINE BY METHYLATED DERIVATIVES OF TRYPTAMINE
British Journal of Pharmacology March 1, 1974 DOI: 10.1111/j.1476-5381.1974.tb09609.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Neurons in the brain stem of rats anesthetized with urethane or decerebrate cats |
| Interventions | N bufotenine acetylcholine noradrenaline glutamate |
| Topics | LSD Psilocybin Serotonin |
| Keywords | Psychotomimetic Tryptamine Pharmacology Hallucinogen Excitatory postsynaptic potential 5-HT Receptor Glutamate receptor |
| Citations | 54 |
| Key findings | Psychotomimetic tryptamines, like LSD, specifically antagonize serotonin excitations of single neurons in the lower brain stem, while non-psychotomimetic 5-MeOT does not. |
Abstract
The actions of 5‐methoxytryptamine (5‐MeOT), N,N ‐dimethyltryptamine (DMT), 5‐hydroxy‐ N,N ‐dimethyltryptamine (bufotenine, 5‐HODMT) and 5‐methoxy‐ N,N ‐dimethyltryptamine (5‐MeODMT), and their interactions with 5‐hydroxytryptamine (5‐HT), acetylcholine, (–)‐noradrenaline, and glutamate were studied by microiontophoresis on single neurones in the brain stem of rats anaesthetized with urethane or decerebrate cats. Like d ‐lysergic 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. In contrast to LSD 25, the psychotomimetic tryptamines only rarely antagonized glutamate effects, indicating that the excitatory 5‐HT receptors and the glutamate receptors on the same neurones may be closely related spatially, but are separate. 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. 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 mimicking actions are unlikely to be due to release of 5‐HT, but are due to direct actions on 5‐HT receptors. 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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 16
- Bufo toads and bufotenine: fact and fiction surrounding an alleged psychedelic. Journal of Psychoactive Drugs 1996
- Drug interactions do not support reduction in serotonin turnover as the mechanism of action of benzodiazepines. Neuropharmacology October 1, 1982
- Effects of diazepam and of serotonin agonists on hyponeophagia in rats. Neuropharmacology April 1, 1982
- Blockade and reversal of 5-methoxy-N,N-dimethyltryptamine-induced analgesia following noradrenaline depletion. Brain Research April 29, 1985
- Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate Journal of Psychopharmacology August 1, 2022
and 11 more in the library
Cites 3
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
- Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide British Journal of Pharmacology September 1, 1968
- Antagonism of 5‐hydroxytryptamine by LSD 25 in the central nervous system: a possible neuronal basis for the actions of LSD 25 British Journal of Pharmacology October 1, 1970