The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain

Eur J Pharmacol. 2007 Mar 22;559(2-3):132-7. doi: 10.1016/j.ejphar.2006.11.075. Epub 2006 Dec 12.


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.

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Biogenic Monoamines / metabolism*
  • Biological Assay / methods
  • Brain / drug effects*
  • Brain / metabolism
  • Designer Drugs / pharmacology*
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Male
  • Norepinephrine / metabolism
  • Psychotropic Drugs / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism


  • Adrenergic Uptake Inhibitors
  • Biogenic Monoamines
  • Designer Drugs
  • Dopamine Uptake Inhibitors
  • Psychotropic Drugs
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Dopamine
  • Norepinephrine