The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.
Fumiko Nagai, Ryouichi Nonaka, Kanako Satoh Hisashi Kamimura
European Journal of Pharmacology March 22, 2007 DOI: 10.1016/j.ejphar.2006.11.075 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Rat brain synaptosomes |
| Interventions | 4-fluoroamphetamine methylone BDB MBDB 2C-I 2C-E 2C-C TMA-2 TMA-6 AMT 5-MeO-AMT DPT 5-MeO-DIPT 5-MeO-MIPT 5-MeO-DMT 3CPP 4MPP |
| Topics | Serotonin |
| Keywords | Neurotransmission neurotransmitters Monoamines Dopamine Norepinephrine Re-uptake Brain chemicals Brain communication Non-medical substances Restricted drugs Phenethylamine Tryptamine Piperazine derivatives Drug effects Disrupt balance Cns Neurological function Alter brain function Brain activity Impact Potent ability Neuropharmacology pharmacology Drug action Drug mechanisms Inhibition Increased release Rat brain cells Novel method |
| Citations | 277 |
| Key points | Phenethylamine and tryptamine derivatives, as well as piperazine derivatives, vary widely in their ability to inhibit monoamine re-uptake and stimulate release, with some designer drugs acting as strongly as restricted drugs on the central nervous system. |
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-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same extent as restricted drugs.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |
Citations in the library
Cited by 109
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. Journal of Medical Toxicology March 1, 2012
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Clinical toxicology of newer recreational drugs Clinical Toxicology October 1, 2011
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
and 104 more in the library
Cites 6
- Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin Synapse 2000
- Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens Journal of Psychoactive Drugs October 1, 1986
- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- Effects of “Legal X” Piperazine Analogs on Dopamine and Serotonin Release in Rat Brain Annals of the New York Academy of Sciences October 1, 2004
- Deaths associated with MBDB misuse. International Journal of Legal Medicine 2000
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