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Forensic Toxicology

, Volume 37, Issue 1, pp 104–112 | Cite as

Effects of aromatic ring-substituted phenethylamines on the release of dopamine and serotonin

  • Minjeong Kim
  • Chae Ha Yang
  • Yong Sup Lee
  • Choon-Gon Jang
  • Seikwan Oh
  • Sooyeun Lee
Original Article

Abstract

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

Keywords

Drug abuse Aromatic ring-substituted phenethylamines New psychoactive substances (NPS) Dopamine (DA) and serotonin (5-HT) DA and 5-HT transporters Microdialysis 

Notes

Acknowledgements

This research was supported by grants from the Ministry of Food and Drug Safety (14182MFDS979 and 16182MFDS417) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1A6A1A03011325).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All animal experiments were approved of the Institutional Animal Care and Use Committee at Daegu Haany University.

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Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of PharmacyKeimyung UniversityDaeguRepublic of Korea
  2. 2.College of Oriental MedicineDaegu Haany UniversityDaeguRepublic of Korea
  3. 3.Department of Life and Nanopharmaceutical SciencesKyung Hee UniversitySeoulRepublic of Korea
  4. 4.Medicinal Chemistry Laboratory, Department of Pharmacy, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea
  5. 5.School of PharmacySungkyunkwan UniversitySuwonRepublic of Korea
  6. 6.School of MedicineEwha Womans UniversitySeoulRepublic of Korea

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