Flakka (alpha-pyrrolidinovalerophenone, α-PVP) is a new psychoactive substance, chemically close to cathinone (the primary psychoactive alkaloid of khat). 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 the societal impact of α-PVP. Today, α-PVP is a tightly controlled substance, currently banned in the US and other countries worldwide. However, the growing abuse and complex 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 CNS drug discovery, including developing novel CNS drugs and identifying their molecular targets.
|Журнал||ACS Chemical Neuroscience|
|Состояние||Опубликовано - 2018|