The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.
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.
Nagai
Fumiko
F
Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, 24-1 Hyakunin-cho 3-chome, Shinjuku-ku, Tokyo, 169-0073 Japan. Fumiko_Nagai@member.metro.tokyo.jp
Nonaka
Ryouichi
R
Satoh Hisashi Kamimura
Kanako
K
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001681:Biological Assay / Q000379:methods; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015198:Designer Drugs / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D015306:Biogenic Monoamines; D015198:Designer Drugs; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D009638:Norepinephrine; D011619:Psychotropic Drugs; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors