TY - JOUR
T1 - Effects of aromatic ring-substituted phenethylamines on the release of dopamine and serotonin
AU - Kim, Minjeong
AU - Yang, Chae Ha
AU - Lee, Yong Sup
AU - Jang, Choon Gon
AU - Oh, Seikwan
AU - Lee, Sooyeun
N1 - Funding Information:
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).
Publisher Copyright:
© 2018, Japanese Association of Forensic Toxicology and Springer Japan KK, part of Springer Nature.
PY - 2019/1/22
Y1 - 2019/1/22
N2 - 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.].
AB - 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.].
KW - Aromatic ring-substituted phenethylamines
KW - DA and 5-HT transporters
KW - Dopamine (DA) and serotonin (5-HT)
KW - Drug abuse
KW - Microdialysis
KW - New psychoactive substances (NPS)
UR - http://www.scopus.com/inward/record.url?scp=85052948103&partnerID=8YFLogxK
U2 - 10.1007/s11419-018-0440-y
DO - 10.1007/s11419-018-0440-y
M3 - Article
AN - SCOPUS:85052948103
SN - 1860-8965
VL - 37
SP - 104
EP - 112
JO - Forensic Toxicology
JF - Forensic Toxicology
IS - 1
ER -