The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain
Abstract
We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-m…
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Tryptamine derivatives cross the blood-brain barrier by active transport via Mg2+ and ATP-dependent uptake.
“Tryptamine derivatives are neurotransmitter precursors that cross the BBB by active transport via Mg2+ and ATP-dependent uptake38–40.”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [40]
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“Tryptamine derivatives are neurotransmitter precursors that cross the BBB by active transport via Mg 2+ and ATP-dependent uptake 38–40 .”
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- Authors
- Nagai, F., Nonaka, R., & Satoh Hisashi Kamimura, K.
- Affiliations
- Tokyo Metropolitan Institute of Public Health (JP)
- Corresponding author
- Nagai, Fumiko
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 559
- Issue
- 2-3
- Pages
- 132-137
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2056758002
- Cited by
- 279
- References
- 1
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 11 · 2022: 13 · 2021: 13 · 2020: 16 · 2019: 12 · 2018: 15 · 2017: 22 · 2016: 15 · 2015: 20 · 2014: 18 · 2013: 30 · 2012: 25
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Solar Energy Technologies Office
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- monoamine neurotransmission, monoamine release, synaptosomes, phenethylamines, tryptamine, methylone, alpha-methyltryptamine, 5-MeO-DMT
- MeSH terms
- Animals, Biological Assay, Brain, Dopamine, Dose-Response Relationship, Drug, Male, Synaptic Transmission, Norepinephrine, Psychotropic Drugs, Serotonin, Synaptosomes, Designer Drugs, Reproducibility of Results, Biogenic Monoamines, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Adrenergic Uptake Inhibitors, Dopamine Uptake Inhibitors, Rats, In Vitro Techniques
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