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

A new small-scale method using rat brain synaptosomes measures how psychoactive drugs affect monoamine re-uptake and release. Phenethylamine derivatives like 4-fluoroamphetamine, methylone, BDB, and MBDB strongly inhibited dopamine, serotonin, and norepinephrine re-uptake; 4-fluoroamphetamine, methylone, and BDB also strongly increased release of all three, while MBDB increased serotonin and norepinephrine release but had little effect on dopamine. Methoxylated phenethylamines (2C-I, 2C-E, 2C-C, TMA-2, TMA-6) only slightly influenced re-uptake and release. The tryptamine AMT was among the strongest re-uptake inhibitors and releasers; 5-MeO-AMT also strongly inhibited re-uptake and increased release. Other tryptamines (DPT, 5-MeO-DIPT, 5-MeO-MIPT, 5-MeO-DMT) inhibited re-uptake but had few effects on release. Piperazine derivatives 3CPP and 4MPP inhibited re-uptake and accelerated release. Results suggest some designer drugs act on the central nervous system as strongly as restricted drugs.

Study at a glance

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.