Biomolecules & Therapeutics  
The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent
Chrislean Jun Botanas1,†, Seong Shoon Yoon2,†, June Bryan de la Peña1, Irene Joy dela Peña1, Mikyung Kim1, Taeseon Woo1, Joung-Wook Seo2, Choon-Gon Jang3, Kyung-Tae Park4, Young Hun Lee4, Yong Sup Lee4, Hee Jin Kim1,* and Jae Hoon Cheong1,*
1Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Seoul 01795, 2Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, 3Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, 4Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
E-mail: (Kim HJ), (Cheong JH)
Tel: +82-2-2339-1609 (Kim HJ), +82-2-2339-1605 (Cheong JH)
Fax: +82-2-2339-1619 (Kim HJ), +82-2-2339-1617 (Cheong JH)
The first two authors contributed equally to this work.
Received: October 27, 2016; Revised: November 10, 2016; Accepted: November 24, 2016; Published online: February 6, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

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) α-piperidinopropiophenone (PIPP) and (2) α-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: Synthetic cathinones, Conditioned place preference, Self-administration, Locomotor sensitization, Abuse potential

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