Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

  • Botanas, Chrislean Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Yoon, Seong Shoon (Center for Safety Pharmacology, Korea Institute of Toxicology) ;
  • de la Pena, June Bryan (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • dela Pena, Irene Joy (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Kim, Mikyung (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Woo, Taeseon (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Seo, Joung-Wook (Center for Safety Pharmacology, Korea Institute of Toxicology) ;
  • Jang, Choon-Gon (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Park, Kyung-Tae (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Lee, Young Hun (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Lee, Yong Sup (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Kim, Hee Jin (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Cheong, Jae Hoon (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
  • Received : 2016.10.27
  • Accepted : 2016.11.24
  • Published : 2017.03.01
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Abstract

A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) ${\alpha}-piperidinopropiophenone$ (PIPP) and (2) ${\alpha}-piperidinopentiothiophenone$ (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.

Keywords

References

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