Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Evaluation of the Abuse Potential of Novel Amphetamine Derivatives with Modifications on the Amine (NBNA) and Phenyl (EDA, PMEA, 2-APN) Sites

  • Custodio, Raly James Perez (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • 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) ;
  • Kwon, Yong Ho (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Kim, Nam Yong (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 : 2017.07.17
  • Accepted : 2017.08.14
  • Published : 2017.11.01
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Abstract

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

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