Flakka: New Dangerous Synthetic Cathinone on the Drug Scene

Abstract

New psychoactive substances are being used as drugs and appear to be quite popular nowadays. Thanks to their specific properties, these drugs create inimitable experiences for intoxicated people. Synthetic cathinones are the most common compounds in these new drugs. Among them, α-pyrrolidopentadione (α-PVP), or “Flakka” (street name), is one of the most famous cathinone-designed drugs. Similar to other synthetic cathinone drugs, α-PVP can effectively inhibit norepinephrine and dopamine transmitters. The adverse reactions of α-PVP mainly include mania, tachycardia, and hallucinations. An increasing number of people are being admitted to emergency wards due to the consequences of their use. This work mainly summarizes the history, synthesis, pharmacology, toxicology, structure–activity relationship, metabolism, clinical process and health risks, poisoning and death, forensic toxicology, and legal status of α-PVP. We hope this review will help bring more attention to the exploration of this substance in order to raise awareness of its negative impacts on humans.

Psychomotor stimulant effects of α-pyrrolidinovalerophenone (αPVP) enantiomers correlate with drug binding kinetics at the dopamine transporter

“…Here, we compared the effects of the classical DAT inhibitor cocaine with the effects of αPVP enantiomers. In humans, αPVP displays a similar onset of action to cocaine but has more long-lasting effects, which may exacerbate the effects of αPVP intoxications (20,60). Our systematic in vitro comparison of cocaine and the two enantiomers of αPVP highlighted substantial differences between the kinetic pro les at DAT, which could also be extended by observations in vivo as a signi cantly prolonged psychomotor effect in mice.…”

“…The pseudo-irreversible kinetics observed in the case of αPVP enantiomers at DAT has important consequences not only in the understanding of psychostimulant effects elicited by αPVP but also in its wide-spread side effects such as delirium states, cardiovascular, and renal complications (20,60). In this study we have focused on the pharmacology of αPVP enantiomers at DAT because of its well-established role of DAT in psychomotor functions (4).…”

“…The drug was originally patented as a CNS (central nervous system) stimulant but never approved for clinical use, and recently appeared on the clandestine drug market as an NPS (17). The use of αPVP in humans induces psychostimulant effects and can cause severe adverse effects including delusions, paranoia, hallucinations, and deleterious cardiovascular effects (20). Importantly, the pharmacological effects of αPVP in humans occur within 10 min after administration of a single dose (15-100 mg) and can last for multiple hours (20,21).…”

“…The use of αPVP in humans induces psychostimulant effects and can cause severe adverse effects including delusions, paranoia, hallucinations, and deleterious cardiovascular effects (20). Importantly, the pharmacological effects of αPVP in humans occur within 10 min after administration of a single dose (15-100 mg) and can last for multiple hours (20,21). A study in humans found that αPVP could still be detected in the bloodstream 6 h after nasal insu ation and 20 h after rectal administration (22), and psychotic episodes have been reported as long as 6 days after consumption (23).…”

Neuropsychopharmacology of Emerging Drugs of Abuse: meta- and para-Halogen-Ring-Substituted α-PVP (“flakka”) Derivatives

“…In fact, the use of novel halogenated synthetic cathinones recently became popular, likely due to their higher potency [10]. In a similar manner, α-Pyrrolidinopentiophenone (α-PVP), more commonly known as "flakka", is one of the most popular synthetic cathinones in the United States and Europe [11,12]. The structure of α-PVP is similar to that of 3,4-methylenedioxypyrovalerone (MDPV), which only differs in the presence of the 3,4-methylenedioxy substitution.…”