Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

  • Abiero, Arvie (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Ryu, In Soo (Center for Safety Pharmacology, Korea Institute of Toxicology) ;
  • Botanas, Chrislean Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Custodio, Raly James Perez (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Sayson, Leandro Val (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Kim, Mikyung (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Lee, Hyun Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Kim, Hee Jin (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Seo, Joung-Wook (Center for Safety Pharmacology, Korea Institute of Toxicology) ;
  • Cho, Min Chang (Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Lee, Kun Won (Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Yoo, Sung Yeun (Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Jang, Choon-Gon (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Yong Sup (Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Cheong, Jae Hoon (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
  • Received : 2019.03.15
  • Accepted : 2019.05.23
  • Published : 2019.12.30
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Abstract

Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to determine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

Keywords

References

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