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Effects of aromatic ring-substituted phenethylamines on the release of dopamine and serotonin
- Effects of aromatic ring-substituted phenethylamines on the release of dopamine and serotonin
- Kim M.; Yang C.H.; Lee Y.S.; Jang C.-G.; Oh S.; Lee S.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Forensic Toxicology
- Forensic Toxicology vol. 37, no. 1, pp. 104 - 112
- Aromatic ring-substituted phenethylamines; DA and 5-HT transporters; Dopamine (DA) and serotonin (5-HT); Drug abuse; Microdialysis; New psychoactive substances (NPS)
- Springer Tokyo
- SCIE; SCOPUS
- Document Type
- Purpose: Significant disturbances of the classical amphetamines on the dopamine (DA) and serotonin (5-HT) systems have been previously reported. However, few studies have been conducted on the effects of new psychoactive phenethylamines on the release of DA and 5-HT. In the present study, the effects of new psychoactive phenethylamines with a variety of aromatic ring substitutions (5-API, 3-FMA, 5-MAPB, and DMMA) on the release of DA and 5-HT were investigated. Methods: Changes of DA, 5-HT and their metabolites in brain microdialysates from rats following exposure to the drugs were examined using a validated liquid chromatography–tandem mass spectrometry method. Their potencies of DA and 5-HT uptake inhibition as well as dopamine transporter (DAT) and serotonin transporter (SERT) binding were also determined. Results: With the exception of DMMA, the drugs markedly affected the extracellular concentration of DA, 5-HT and/or their metabolites in rats and acted as potent inhibitors for DAT and/or SERT. Especially, 5-API potently induced the nonselective release of both DA and 5-HT, which was strongly correlated with a high degree of uptake inhibition and binding affinity to DAT and SERT. The 3-FMA, a methamphetamine analog with a halogen-substituted benzene, induced greater 5-HT release than DA. Conclusions: We found that new psychoactive phenethylamines, with a variety of aromatic ring substitutions, affected the extracellular levels of DA, 5-HT, and/or their metabolites in the nucleus accumbens of rats to varying degrees and in different ways. The current results may assist further research into monoamine neurotransmitter-related mechanisms of new psychoactive phenethylamines. Graphical abstract: [Figure not available: see fulltext.]. © 2018, Japanese Association of Forensic Toxicology and Springer Japan KK, part of Springer Nature.
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