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Alpha-pyrrolidinovalerophenone (α-PVP) is a designer drug, the mechanism of action of which resembles that of cocaine and amphetamine. New data about the side effects of α-PVP are emerging. We present a case report of an acute ischemic stroke following the recreational use of α-PVP. The ischemic lesions were located in the middle cerebral artery and deep watershed areas of the left cerebral hemisphere. Occupational therapy and physiotherapy were initiated, and the patient was discharged with only a mild right hemiparesis.

Alpha-pyrrolidinovalerophenone (α-PVP) is a designer drug, the mechanism of action of which resembles that of cocaine and amphetamine. New data about the side effects of α-PVP are emerging. We present a case report of an acute ischemic stroke following the recreational use of α-PVP. The ischemic lesions were located in the middle cerebral artery and deep watershed areas of the left cerebral hemisphere. Occupational therapy and physiotherapy were initiated, and the patient was discharged with only a mild right hemiparesis. [ABSTRACT FROM AUTHOR]

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.

There are many challenges facing healthcare professionals. One such challenge is the continuous introduction of new synthetic drugs. Synthetic drugs pose many difficulties to providers, including identification of the drug ingested, management of symptoms, ensuring safety of the patient and his or her environment, and continual monitoring after the initial symptoms, because synthetic cathinones have many long-term effects on an individual. One such synthetic drug, flakka, is a potent second-generation synthetic cathinone. Because flakka inhibits the reuptake of norepinephrine and dopamine, which are involved in one's perception of pleasure, it causes inflated feelings and also causes signs and symptoms of psychosis. Flakka also induces various exaggerated symptoms, such as feelings of incredible strength, disorientation, aggression, and altered thought processes, and also can cause hyperthermia, coma, and death. Healthcare professionals need to understand the nature of flakka ingestion, the various symptoms a user may exhibit, and the long-term symptoms a person may have once the acute recovery phase has ended. Once the initial phase of ingestion is over and the patient is medically stabilized, the patient may experience signs and symptoms of psychosis or other psychiatric disorders. It is paramount that healthcare professionals are able to recognize the signs and symptoms of flakka ingestion, know the steps to take to ensure safety of the patient and those around him or her, and also know how to facilitate the patient's recovery. [ABSTRACT FROM AUTHOR]

α-Pyrrolidinovalerophenone (α-PVP), a dangerous designer drug, is now being marketed around the world as a harmless `bath salt', when in reality it is a powerful β-ketone phenethylamine stimulant. A sample of the free base from a recent law-enforcement seizure was crystallized as the HCl salt [systematic name: 1-(1-oxo-1-phenylpentan-2-yl)pyrrolidin-1-ium chloride 0.786-hydrate], C15H22NO+·Cl−·0.786H2O. In the crystal structure, the propyl chain is nearly perpendicular to both the phenyl ring and the carbonyl group. The hydrogen-bonding scheme involves the quaternary N atom, the Cl− anion and the partially occupied (0.786) water molecule, forming centrosymmetric dimers. [ABSTRACT FROM AUTHOR]

'Flakka' is the street name for the synthetic cathinone α-pyrrolidinopentiophenone (α-PVP). Although it was developed by Boehringer Ingelheim as a central nervous system stimulant and pressor agent in the 1960s, it entered in the drug arena at an accelerated rate during the last 4 years causing intoxications, fatal or not. α-PVP is abused in Europe, as well as in the United States and Japan, as a substituent of 3, 4-methylenedioxypyrovalerone, and recently scheduled by the United States Drug Enforcement Administration, possessing similar pharmacological action to that of the latter. It can be easily manufactured and purchased through the Internet or in retail shops and is usually sold as 'bath salts'. The aim of this review is to summarize the current knowledge of this drug concerning its chemistry, synthesis, metabolism, pharmacology, and toxicology. 'Flakka' related cases, published or reported, including fatalities or intoxications, as well as seizures are reviewed. The existing analytical methodologies for the determination of α-PVP in biological and postmortem samples are summarized, and its current legal status is reported. [ABSTRACT FROM AUTHOR]

The term "synthetic drugs" is no longer a non-specific pharmacological phrase but one that describes a group of "designer drugs" which are responsible for global morbidity and mortality. In 2009, the United States (US) began experiencing the rapid emergence of these compounds and by 2010, cannabinoids (e.g. "K2," "spice") and cathinones (e.g. "bath salts," "flakka") had become known on the street as the new designer drugs of choice. By definition, a "designer drug" is an analogue of a controlled substance which allows the user to experience the same, or similar, feelings as that from the controlled substance. With many derivitizations possible, new analogues may not be scheduled in the Controlled Substance Act (CSA). This permits the user to obtain a "legal high" with less fear of submitting a positive drug sample or other legal consequences. This is of paramount importance to our current synthetic drug abuse crisis as the Drug Enforcement Administration (DEA) is being inundated with new analogues at a rate faster than their ability to schedule these compounds within the CSA. Synthetic drugs represent a considerable threat to the user as they may experience a desired euphoria, but with the risk of concomitant central nervous system (CNS) stimulation resulting in tachycardia, hypertension, agitation, hyperthermia, seizures, rhabdomyolysis, excited delirium and violent behavior. Medical professionals attempting to treat these patients lack information regarding the chemical composition of these drugs and thereby can only offer symptom-based supportive care. However, treatment is often further hampered by the violent behavior manifested by these patients and protective actions needed by the medical team. The synthetic drug abuse crisis reflects a number of similarities to a viral pandemic. The disease has spread rapidly throughout multiple countries via the assistance of a global carrier (the internet), with the virus mutation (analogue production) occurring at a pace that makes it difficult for agencies to quickly identify and regulate. Therefore, as in any disease outbreak, it becomes imperative for healthcare providers, scientists and law enforcement agencies to foster a mutual relationship of information exchange. Establishing an international database containing chemical structures of synthetic drugs, and their analogues, would allow for more prompt identification and regulation by policy makers looking to deter synthetic drug abuse worldwide. [ABSTRACT FROM AUTHOR]

Synthetic cathinones are a class of novel psychoactive substances. a- Pyrrolidinopentiophenone (α-PVP), or "Flakka", is one of these substances. Users often present acutely psychotic or agitated. We present the case of a 20-year-old male without prior psychiatric history who was brought to the hospital by his family because of increasingly bizarre and erratic behavior after reported ingestion of Flakka. What ensued was a prolonged course of psychosis and severe catatonia. Synthetic cathinones are thought to cause catatonia in approximately 1% of cases. Awareness of the possible presentations associated with α-PVP intoxication is increasingly important and should be further explored, as they can have important implications in setting expectations for care. Additionally, providers should have a low threshold for asking patients about bath salt ingestion. [ABSTRACT FROM AUTHOR]

Clandestine chemists are currently exploiting the pyrrolidinophenone scaffold to develop new designer drugs that carry the risk of abuse and overdose. These drugs promote addiction through the rewarding effects of increased dopaminergic neurotransmission. 3,4-Methylenedioxypyrovalerone (MDPV) and its analogs are illicit psychostimulants of this class that are ∼50-fold more potent than cocaine at inhibiting the human dopamine transporter (hDAT). In contrast, MDPV is a weak inhibitor at both the human serotonin transporter (hSERT) and, as it is shown here, the Drosophila melanogaster DAT (dDAT). We studied three conserved residues between hSERT and dDAT that are unique in hDAT (A117, F318, and P323 in dDAT), and one residue that is different in all three transporters (D121 in dDAT). hDAT residues were replaced in the dDAT sequence at these positions using site-directed mutagenesis and stable cell lines were generated expressing these mutant transporters. The potencies of MDPV and two of its analogs were determined using a Ca2+-mobilization assay. In this assay, voltage-gated Ca2+ channels are expressed to sense the membrane electrical depolarization evoked when dopamine is transported through DAT. Each individual mutant slightly improved MDPV's potency, but the combination of all four increased its potency ∼100-fold (2 log units) in inhibiting dDAT activity. Molecular modeling and docking studies were conducted to explore the possible mode of interaction between MDPV and DAT in silico. Two of the studied residues (F318 and P323) are at the entrance of the S1 binding site, whereas the other two (A117 and D121) face the aryl moiety of MDPV when bound to this site. Therefore, these four non-conserved residues can influence MDPV selectivity not only by stabilizing binding, but also by controlling access to its binding site at DAT. • Analogs of MDPV are frequent-appearing designer drugs. • Four non-conserved residues of hDAT account for MDPV high potency. • These four residues are marginally implicated in dopamine recognition. • Access and interaction with the S1 site might control MDPV selectivity at DAT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Flakka, as the newest member of the synthetic cathinone group, is a substance with serious cardiovascular, neurological, psychiatric, infectious effects and addictive potential. There are only a few case reports and laboratory studies in the literature and there is no dermatological side effects reported yet. We present the first Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN) overlap case after Flakka use. [ABSTRACT FROM AUTHOR]

α-Pyrrolidinovalerophenone (α-PVP, 7) is an illegal synthetic stimulant that is being sold on the clandestine market as "flakka" and "gravel". The potent pharmacological effects of α-PVP are presumably mediated by inhibition of dopamine uptake at the dopamine transporter (DAT). However, little is known about how structural modification of α-PVP influences activity at DAT. Eleven analogs of α-PVP were synthesized and examined for their ability to inhibit uptake of [(3)H]dopamine and [(3)H]serotonin in rat brain synaptosomes. None of the analogs significantly inhibited [(3)H]serotonin uptake when tested at 10 μM at the serotonin transporter (SERT). All of the analogs behaved as DAT reuptake inhibitors, but potencies varied over a >1500-fold range. Potency was primarily associated with the nature of the α-substituent, with the more bulky substituents imparting the highest potency. Expansion of the pyrrolidine ring to a piperidine reduced potency up to 10-fold, whereas conformational constraint in the form of an aminotetralone resulted in the least potent compound. Our study provides the first systematic and comparative structure-activity investigation on the ability of α-PVP analogs to act as inhibitors of DAT.