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DARK Classics in Chemical Neuroscience: α-Pyrrolidinovalerophenone ("Flakka").
ACS Chem Neurosci. 2019 01 16; 10(1):168-174.AC

Abstract

Flakka (alpha-pyrrolidinovalerophenone, α-PVP) is a new psychoactive substance, chemically close to cathinone, the primary psychoactive alkaloid of khat (Catha edulis). Like other synthetic cathinones, α-PVP is a potent inhibitor of the dopamine and norepinephrine transporters. Its robust clinical effects include hallucinations, arousal, aggression/violence, and euphoria. In animal models, α-PVP evokes hyperlocomotion and aberrant/stereotypic behaviors. Here, we discuss the history, synthesis, pharmacological mechanisms, metabolism, abuse potential, and societal impact of α-PVP. Today, α-PVP is a tightly controlled substance, currently banned in the United States and other countries worldwide. However, the growing abuse and complex central nervous system (CNS) effects of α-PVP remain poorly understood, necessitating further pharmacological and pharmacogenetic studies of this drug. Its interesting pharmacological profile (co-inhibition of dopamine and norepinephrine, but not serotonin, transporters) also calls for further studies of α-PVP in animal models, to dissect serotonergic from other monoaminergic mechanisms of action of drugs of abuse. Finally, screening α-PVP and related compounds in vivo may foster discovery of new CNS drugs, including developing novel CNS drugs and identifying their molecular targets.

Authors+Show Affiliations

Ural Federal University , Ekaterinburg 620002 , Russia.Ural Federal University , Ekaterinburg 620002 , Russia.Institute of Experimental Medicine, Almazov National Medical Research Centre , Ministry of Healthcare of Russian Federation , St. Petersburg 194156 , Russia. Institute of Translational Biomedicine , St. Petersburg State University , St. Petersburg 199034 , Russia.Ural Federal University , Ekaterinburg 620002 , Russia.School of Pharmacy , Southwest University , Chongqing 400700 , China. Anatomy and Physiological Laboratory , Ural Federal University , Ekaterinburg 620002 , Russia. ZENEREI Research Center , Slidell , Louisiana 70458 , United States. Laboratory of Biological Psychiatry, ITBM , St. Petersburg State University , St. Petersburg 199034 , Russia. Almazov National Medical Research Centre , Ministry of Healthcare of Russian Federation , St. Petersburg 194156 , Russia. Scientific Research Institute of Physiology and Basic Medicine , Novosibirsk 630117 , Russia. Granov Russian Scientific Center of Radiology and Surgical Technologies , Ministry of Healthcare of Russian Federation , St. Petersburg 197758 , Russia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

30384587

Citation

Kolesnikova, Tatiana O., et al. "DARK Classics in Chemical Neuroscience: α-Pyrrolidinovalerophenone ("Flakka")." ACS Chemical Neuroscience, vol. 10, no. 1, 2019, pp. 168-174.
Kolesnikova TO, Khatsko SL, Demin KA, et al. DARK Classics in Chemical Neuroscience: α-Pyrrolidinovalerophenone ("Flakka"). ACS Chem Neurosci. 2019;10(1):168-174.
Kolesnikova, T. O., Khatsko, S. L., Demin, K. A., Shevyrin, V. A., & Kalueff, A. V. (2019). DARK Classics in Chemical Neuroscience: α-Pyrrolidinovalerophenone ("Flakka"). ACS Chemical Neuroscience, 10(1), 168-174. https://doi.org/10.1021/acschemneuro.8b00525
Kolesnikova TO, et al. DARK Classics in Chemical Neuroscience: α-Pyrrolidinovalerophenone ("Flakka"). ACS Chem Neurosci. 2019 01 16;10(1):168-174. PubMed PMID: 30384587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DARK Classics in Chemical Neuroscience: α-Pyrrolidinovalerophenone ("Flakka"). AU - Kolesnikova,Tatiana O, AU - Khatsko,Sergey L, AU - Demin,Konstantin A, AU - Shevyrin,Vadim A, AU - Kalueff,Allan V, Y1 - 2018/11/26/ PY - 2018/11/6/pubmed PY - 2020/2/7/medline PY - 2018/11/3/entrez KW - Zebrafish KW - anxiety behavior KW - drugs of abuse KW - sedation KW - synthetic cathinone KW - α-PVP SP - 168 EP - 174 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 10 IS - 1 N2 - Flakka (alpha-pyrrolidinovalerophenone, α-PVP) is a new psychoactive substance, chemically close to cathinone, the primary psychoactive alkaloid of khat (Catha edulis). Like other synthetic cathinones, α-PVP is a potent inhibitor of the dopamine and norepinephrine transporters. Its robust clinical effects include hallucinations, arousal, aggression/violence, and euphoria. In animal models, α-PVP evokes hyperlocomotion and aberrant/stereotypic behaviors. Here, we discuss the history, synthesis, pharmacological mechanisms, metabolism, abuse potential, and societal impact of α-PVP. Today, α-PVP is a tightly controlled substance, currently banned in the United States and other countries worldwide. However, the growing abuse and complex central nervous system (CNS) effects of α-PVP remain poorly understood, necessitating further pharmacological and pharmacogenetic studies of this drug. Its interesting pharmacological profile (co-inhibition of dopamine and norepinephrine, but not serotonin, transporters) also calls for further studies of α-PVP in animal models, to dissect serotonergic from other monoaminergic mechanisms of action of drugs of abuse. Finally, screening α-PVP and related compounds in vivo may foster discovery of new CNS drugs, including developing novel CNS drugs and identifying their molecular targets. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/30384587/DARK_Classics_in_Chemical_Neuroscience:_α_Pyrrolidinovalerophenone__"Flakka"__ L2 - https://doi.org/10.1021/acschemneuro.8b00525 DB - PRIME DP - Unbound Medicine ER -