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.

PY - 2019/1/16

Y1 - 2019/1/16

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.

AB - 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.

KW - anxiety behavior

KW - drugs of abuse

KW - sedation

KW - synthetic cathinone

KW - Zebrafish

KW - α-PVP

KW - DRUG

KW - DEATH

KW - PVP

KW - BODY-FLUIDS

KW - BATH SALTS

KW - alpha-PVP

KW - METABOLISM

KW - SOLID TISSUES

KW - POSTMORTEM DISTRIBUTION

KW - MDPV

UR - http://www.scopus.com/inward/record.url?scp=85057435840&partnerID=8YFLogxK

U2 - 10.1021/acschemneuro.8b00525

DO - 10.1021/acschemneuro.8b00525

M3 - Review article

AN - SCOPUS:85057435840

VL - 10

SP - 168

EP - 174

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 1

ER -