generation run 2026-04-26
67 min completedmodel pipeline-v5plan not recordedrun/99794152…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- psychological_dependence_high_but_no_taper_basis
Reproduce
- inputs
- 38 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | pyrrolidinopentiophenone forensic detection blood | 7 | 4 | Forensic case data relevant to toxicity section |
| 2 | PubMed | get_pubmed_article 33142953 | 1 | 1 | Comprehensive review article - primary reference for historical and regulatory information |
| 3 | PubChem | alpha-PVP | 1 | 1 | Primary chemical identity verification for A-PVP |
| 4 | PubMed | alpha-PVP DAT NET SERT reuptake inhibition monoamine transporter | 15 | 9 | Binding affinity, SAR, self-administration, and pharmacokinetics papers |
| 5 | PubMed | synthetic cathinone pyrrolidinopentiophenone metabolism pharmacokinetics urine | 1 | 1 | Forensic distribution data relevant to pharmacokinetics section |
| 6 | PubMed | alpha-PVP alpha-pyrrolidinopentiophenone pharmacology | 15 | 9 | Core pharmacology and toxicology papers directly relevant to A-PVP article |
| 7 | PubMed | get_pubmed_article 40672373 | 1 | 1 | Only published human pharmacology study for α-PVP intranasal route |
| 8 | PubMed | get_pubmed_article 31724254 | 1 | 1 | Critical stereochemistry data - explains which enantiomer drives pharmacological activity |
| 9 | PubMed | get_pubmed_article 39789240 | 1 | 1 | Only published human pharmacokinetic data for α-PVP |
| 10 | PubMed | alpha-PVP cathinone DAT NET SERT microdialysis nucleus accumbens | 4 | 2 | Reward pathway mechanism and stereochemistry papers |
| 11 | PubMed | alpha-PVP cathinone dopamine rat self-administration reward | 3 | 4 | Key pharmacology and PK papers for α-PVP specifically |
| 12 | WebSearch | alpha-PVP DEA Schedule I scheduling date Federal Register | 10 | 1 | Primary source for US legal status |
| 13 | ClinicalTrials.gov · absence | alpha-PVP pyrrolidinopentiophenone stimulant | 0 | 0 | No active or completed clinical trials; confirms absence of therapeutic development |
| 14 | PubMed | get_pubmed_article PMID 24668489 | 1 | 1 | Earliest documented US detection of α-PVP in urine specimens |
| 15 | WebSearch | alpha-PVP EU EMCDDA scheduling Japan China ban 2014 2015 | 10 | 4 | International legal status data |
| 16 | OpenAlex | alpha-PVP pyrrolidinovalerophenone dopamine transporter inhibition potency | 8 | 4 | High-impact reviews and in vivo pharmacology data |
| 17 | PubMed/PubChem | PMID correction: 39561949 vs 39561469 for Kriikku et al. 2024 | 1 | 1 | Error correction for citation registry |
| 18 | WebSearch | alpha-PVP Australia TGA Schedule 9 prohibited substance April 2018 | 10 | 1 | Australia legal status confirmation |
93 claims by section — every cited sentence, checked against its source
safety33 · 27 ok
The acute toxicity profile follows the sympathomimetic toxidrome: tachycardia, hypertension, tachypnea, hyperthermia, seizures, psychomotor agitation, rhabdomyolysis, and acute kidney injury.supported
MDPV (closely related to α-PVP) intoxication characterized by profound toxicities: tachycardia, hypertension, arrhythmias, hyperthermia, rhabdomyolysis, seizures, stroke, death. j.amjmed.2012.02.019
The acute toxicity profile follows the sympathomimetic toxidrome: tachycardia, hypertension, tachypnea, hyperthermia, seizures, psychomotor agitation, rhabdomyolysis, and acute kidney injury.supported
Via direct and indirect activation of the sympathetic nervous system, synthetic cathinones cause tachycardia, hypertension, hyperthermia, myocardial infarction, and death. j.jemermed.2013.11.104
In 34 fatal poisoning cases in Finland (2018–2023), the median femoral blood α-PVP concentration was 0.18 mg/L (range: 0.03–2.6 mg/L)supported
Median α-PVP femoral blood concentration in fatal poisonings: 0.18 mg/L (range 0.03–2.6 mg/L). 34 fatal poisonings (29%). j.forsciint.2024.112297
This wide range reflects extensive polydrug involvement rather than an intrinsic lethal threshold — only 1.7% of fatal synthetic cathinone cases involved α-PVP as the sole substancesupported
Concomitant drugs in 69–92% of cases. In only 1.7% were SCs the sole drug. j.forsciint.2024.112297
In 29% of α-PVP-positive deaths, α-PVP was implicated in the cause of death.supported
34 fatal poisonings (29%). j.forsciint.2024.112297
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Direct myotoxicity has been demonstrated in vitro: α-PVP impairs mitochondrial function in C2C12 myoblasts at concentrations of 50–2,000 µM, inhibiting mitochondrial Complex I, depleting ATP, and increasing mitochondrial superoxidesupported
α-PVP directly myotoxic to C2C12 myoblasts: impairs cell membrane integrity, depletes ATP, increases mitochondrial superoxide (50–2000 µM range). Inhibits mitochondrial complex I specifically. ijms20071561
Clinical case reports document rhabdomyolysis-induced acute kidney injury as a prominent feature of severe pyrovalerone-class toxicity.supported
IV bath salts (MDPV-class) causing sympathomimetic syndrome, choreoathetosis, AKI (creatinine 15.2 mg/dL), rhabdomyolysis (CK 4457 IU/dL). pmid:24356039
Repeated α-PVP administration (20 mg/kg i.p. × 10 days) significantly impaired spatial learning and memory in Wistar rats through brain mitochondrial dysfunction — increased ROS production, collapsed mitochondrial membrane potential, and cytochrome c releasesupported
α-PVP (20 mg/kg) significantly impaired spatial learning/memory and brain mitochondrial function in Wistar rats; increased ROS, lipid peroxidation, collapsed MMP. j.taap.2023.116497
In 118 post-mortem Finnish cases (2018–2023), α-PVP was present with opioids, stimulants, or sedatives in 69–92% of casessupported
136 findings of α-PVP, α-PHP, or α-PiHP in 118 death cases in Finland (2018–2023)... Concomitant drugs in 69–92% of cases. j.forsciint.2024.112297
Mixed synthetic cathinone poisoning dramatically elevates toxicity risk compared to single-substance exposure.supported
polydrug use increased SC toxicity. All fatal cases associated with multiple organ failure. bkab119
Paranoia, psychotic episodes, hallucinations, aggression, and severe anxiety are documented in clinical case series and epidemiological datasupported
Study identifying risk factors and predictors of psychotic disorders in synthetic cathinone users. jnevro2023123051153
Paranoia, psychotic episodes, hallucinations, aggression, and severe anxiety are documented in clinical case series and epidemiological datasupported
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 (Flakka). ijms21218185
Claim in safety — inconclusiveinconclusiveworking →
Behavioral toxicity extends to loss of behavioral control: erratic public behavior, aggression, and inability to safely operate motor vehicles were documented during the 2014–2015 "Flakka" epidemic and in Japanese traffic accident reports.supported
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 (Flakka). ijms21218185
Behavioral toxicity extends to loss of behavioral control: erratic public behavior, aggression, and inability to safely operate motor vehicles were documented during the 2014–2015 "Flakka" epidemic and in Japanese traffic accident reports.supported
Caused traffic accidents in Japan. jts.42.539
Chronic use produces neuroinflammation with sex-dependent patterns — males develop widespread brain pro-inflammatory cytokine increases (IL-1α, IL-1β, IL-6, CCL2, TNF-α), while females show predominantly peripheral cytokine elevation.supported
α-PVP self-administration produced sex-dependent neuroinflammatory patterns; males showed widespread brain cytokine increases, females showed more plasma increases. j.neuro.2021.11.002
Claim in safety — not_supportednot supportedworking →
Reinforcing effectiveness directly correlates with DAT/SERT selectivity, and α-PVP's extreme ratio predicts maximal compulsive-use liabilitysupported
Reinforcing effectiveness correlated with selectivity for DAT over SERT... rank order for selectivity at DAT over SERT: α-PVP > α-PPP > MDPV... s41386-018-0209-3
Claim in safety — inconclusiveinconclusiveworking →
Studies of the closely related compound MDPV document DAT downregulation, ΔFosB induction, and CDK5 increases persisting post-withdrawalsupported
MDPV sensitization: DAT downregulation, ΔFosB induction, CDK5 and TH changes persisting post-withdrawal. j.neuropharm.2018.10.005
In Finnish post-mortem data, 69–92% of α-PVP-positive cases involved concomitant opioids, stimulants, or sedativessupported
Concomitant drugs in 69–92% of cases. j.forsciint.2024.112297
Mixed synthetic cathinone poisoning case series confirm dramatically elevated toxicity.supported
polydrug use increased SC toxicity. All fatal cases associated with multiple organ failure. bkab119
Alcohol: Ethanol pre-exposure differentially modifies α-PVP reward/aversion balance in rats, altering both rewarding and aversive effectssupported
Ethanol history modifies behavioral response to α-PVP; relevant to alcohol-α-PVP interaction assessment. j.pbb.2021.173286
Other stimulants: Co-administration of α-PVP with MDPV produced significantly greater locomotor activation than either drug alone, particularly in females, with the mixture producing conditioned place preference that α-PVP alone did not generate at low doses.supported
MDPV and α-PVP mixture produced significantly greater locomotor activation than either drug alone in females. α-PVP alone failed to produce CPP in either sex, while MDPV and the mixture did. j.pbb.2024.173907
Cardiovascular disease: Pre-existing tachyarrhythmias, hypertension, coronary artery disease, and structural heart disease represent absolute contraindications. α-PVP produces dose-dependent increases in heart rate and blood pressure, and cardiovascular collapse is a component of fatal sympathomimetic toxidrome.supported
S-α-PVP is the active enantiomer responsible for most neurochemical, behavioral, and cardiovascular effects of the racemate. adb.12842
Cardiovascular disease: Pre-existing tachyarrhythmias, hypertension, coronary artery disease, and structural heart disease represent absolute contraindications. α-PVP produces dose-dependent increases in heart rate and blood pressure, and cardiovascular collapse is a component of fatal sympathomimetic toxidrome.supported
Via direct and indirect activation of the sympathetic nervous system, synthetic cathinones cause tachycardia, hypertension, hyperthermia, myocardial infarction, and death. j.jemermed.2013.11.104
Psychotic disorders and bipolar disorder: History of psychosis or bipolar disorder represents an absolute contraindication given α-PVP's documented association with acute psychotic episodes, paranoid ideation, and mania.supported
Study identifying risk factors and predictors of psychotic disorders in synthetic cathinone users. jnevro2023123051153
Psychotic disorders and bipolar disorder: History of psychosis or bipolar disorder represents an absolute contraindication given α-PVP's documented association with acute psychotic episodes, paranoid ideation, and mania.supported
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 (Flakka). ijms21218185
Claim in safety — inconclusiveinconclusiveworking →
Renal impairment: Rhabdomyolysis-induced acute kidney injury is a prominent feature of severe α-PVP toxicitysupported
Direct mitochondrial toxicity contributes to rhabdomyolysis beyond sympathomimetic effects. ijms20071561
Renal impairment: Rhabdomyolysis-induced acute kidney injury is a prominent feature of severe α-PVP toxicitysupported
AKI (creatinine 15.2 mg/dL), rhabdomyolysis (CK 4457 IU/dL). pmid:24356039
pharmacology13 · 12 ok
The compound is a pure transporter blocker — it inhibits monoamine reuptake without promoting substrate release, distinguishing it mechanistically from amphetamine-type cathinones such as mephedrone and methcathinone.supported
Comprehensive review of in vitro methods used to characterize cathinones at monoamine transporters, including uptake inhibition, release, voltage clamp, and Ca2+ mobilization assays. bs.apha.2023.09.001
The compound is a pure transporter blocker — it inhibits monoamine reuptake without promoting substrate release, distinguishing it mechanistically from amphetamine-type cathinones such as mephedrone and methcathinone.supported
α-PVP exerts strong psychostimulatory effects via high-potency DAT and NET inhibition with negligible SERT activity. Enhancement of dopaminergic neurotransmission plays dominant role. s11419-018-0409-x
The DAT/SERT inhibition ratio exceeds 4,030, making α-PVP among the most dopamine-selective compounds ever characterized in the cathinone classsupported
α-PVP DAT/SERT inhibition ratio >4030. Used as reference compound for method validation. dta.3547
This extreme selectivity places α-PVP at the far end of the cathinone selectivity spectrum, where DAT dominance correlates directly with reinforcing efficacy and abuse potential.supported
rank order for selectivity at DAT over SERT: α-PVP > α-PPP > MDPV > MDPBP > MDPPP > cocaine. Reinforcing effectiveness correlated with selectivity for DAT over SERT. s41386-018-0209-3
At higher non-cytotoxic concentrations, partially irreversible inhibition of neuronal activity has been observed in multi-electrode array (MEA) assayssupported
High concentrations produced partially irreversible inhibition of neuronal activity. fnins.2020.00009
IC₅₀ values at human DAT, NET, and SERT have been confirmed across fluorescence-based and radiometric assay platforms, with consistent results indicating sub-micromolar to low micromolar potency at DAT and NET and minimal SERT activitysupported
IC50 values for α-PVP at hDAT, hNET, hSERT determined using fluorescent assay in HEK293 cells. Results consistent with radiometric assays. j.tiv.2017.05.010
None of 11 α-PVP analogs tested significantly inhibited [³H]serotonin uptake at concentrations up to 10 µM.supported
None significantly inhibited SERT at 10 μM. acschemneuro.5b00160
Pharmacokinetic data for α-PVP in humans are limited to a single naturalistic observational study of intranasal administrationsupported
An observational non-controlled naturalistic study on 8 healthy volunteers was conducted to assess the α-PVP and β-OH-α-PVP concentrations in oral fluid and urine, after snorting 10 mg or 20 mg of α-PVP. s12248-024-01012-7
Tmax of 47–60 minutes was notably later than non-pyrrolidine synthetic cathinones, possibly reflecting pyrrolidine ring characteristics affecting absorption or distribution.supported
α-PVP reached a mean Cmax of 762 ng/mL at 1h after 10mg administration s12248-024-01012-7
The primary metabolic pathway involves oxidative opening of the pyrrolidine ring, producing an N-butanoic acid metabolite as the most abundant urinary species (also detected as a glucuronide). β-OH-α-PVP was identified as a minor metabolitesupported
the pyrrolidine ring oxidative opening produced the most abundant urinary metabolite (N-butanoic acid), independently from dose. s12248-024-01012-7
Earlier analysis of US urine specimens confirmed excretion of unchanged α-PVP alongside pyrrolidine ring degradation products — primary amine formation followed by carbonyl reduction.supported
α-PVP (PVP) detected in US urine specimens (2011-2013); metabolic profile: pyrrolidine ring degradation to primary amine followed by carbonyl reduction. Can be detected unchanged or as metabolites. bku021
Claim in pharmacology — inconclusiveinconclusiveworking →
Rat pharmacokinetic studies have been conducted, including evaluation of an anti-α-PVP vaccine that reduced CNS penetration.supported
Novel studies determined the pharmacokinetics (PK) of α-PVP in rats and evaluated the effects of an α-PVP vaccine on the PK profile. jpps31832
neuroscience11 · 10 ok
Repeated high-dose α-PVP administration (20 mg/kg i.p. × 10 days) impairs spatial learning and memory in rats through brain mitochondrial dysfunction — increased reactive oxygen species, collapsed mitochondrial membrane potential, and cytochrome c releasesupported
α-PVP (20 mg/kg) significantly impaired spatial learning/memory and brain mitochondrial function in Wistar rats; increased ROS, lipid peroxidation, collapsed MMP. j.taap.2023.116497
This mechanism parallels the direct mitochondrial impairment documented in skeletal muscle cells, suggesting mitochondrial vulnerability as a shared toxicity pathway across organ systems.supported
α-PVP directly myotoxic to C2C12 myoblasts: impairs cell membrane integrity, depletes ATP, increases mitochondrial superoxide (50–2000 µM range). Inhibits mitochondrial complex I specifically. ijms20071561
While α-PVP-specific sensitization data are limited, closely related MDPV produces lasting neuroadaptive changes following sensitization regimens: DAT downregulation, ΔFosB induction, and CDK5 increases persisting into withdrawalsupported
MDPV sensitization: DAT downregulation, ΔFosB induction, CDK5 and TH changes persisting post-withdrawal. j.neuropharm.2018.10.005
Dose-response threshold for cognitive neurotoxicity: At what cumulative exposure does mitochondrial-mediated cognitive impairment emerge in humans? Animal data suggest a threshold effect (5 mg/kg producing no impairment, 20 mg/kg producing significant deficits), but human translation is unknown.supported
α-PVP (20 mg/kg) significantly impaired spatial learning/memory and brain mitochondrial function in Wistar rats... Lower doses (5 mg/kg) did not alter spatial learning/memory. j.taap.2023.116497
Claim in neuroscience — not_supportednot supportedworking →
Conditioned place preference dose-dependence: α-PVP failed to produce conditioned place preference at 1 mg/kg but did produce CPP at 25 mg/kg. The dose-response relationship for conditioned reward and its relationship to self-administration behavior remains uncharacterized.supported
α-PVP (25 mg/kg, 3 days) induced CPP in C57BL/6j mice. jts.42.539
Administration increases extracellular dopamine in the nucleus accumbens shell immediately following dosing in mice and elevates striatal dopamine in vivo in rodentssupported
Increased extracellular dopamine in nucleus accumbens shell immediately after administration. jts.42.539
This dopamine elevation activates downstream signaling cascades: repeated administration induces phosphorylation of CREB (cAMP response element-binding protein) in the nucleus accumbens shell, a canonical molecular marker of reward pathway engagement and drug-induced neuroplasticity.supported
Increased phospho-CREB in nucleus accumbens. jts.42.539
Female rats showed a different pattern, with cytokine increases predominantly in plasma rather than brain tissuesupported
males showed widespread brain cytokine increases, females showed more plasma increases. j.neuro.2021.11.002
Sex differences in neurotoxicity: Female rats show greater locomotor sensitivity to α-PVP and different neuroinflammatory patterns. Whether these sex differences translate to differential human vulnerability is unknown.supported
Sex differences in α-PVP effects on taste avoidance, place preference, hyperthermia and locomotor activity in rats j.pbb.2019.172762
Sex differences in neurotoxicity: Female rats show greater locomotor sensitivity to α-PVP and different neuroinflammatory patterns. Whether these sex differences translate to differential human vulnerability is unknown.supported
α-PVP self-administration produced sex-dependent neuroinflammatory patterns; males showed widespread brain cytokine increases, females showed more plasma increases. j.neuro.2021.11.002
summary10 · 9 ok
α-Pyrrolidinopentiophenone (α-PVP, also known as "Flakka") is a synthetic cathinone stimulant distinguished by extreme selectivity for the dopamine transporter (DAT), with a DAT/SERT inhibition ratio exceeding 4,030 — among the highest of any characterized psychoactive compoundsupported
α-PVP DAT/SERT inhibition ratio >4030. Used as reference compound for method validation. dta.3547
Claim in summary — not_supportednot supportedworking →
Despite over 40 published primary studies, the first controlled human pharmacokinetic data were not published until 2025, and no clinical trials have been conductedpartially supported
An observational non-controlled naturalistic study on 8 healthy volunteers was conducted to assess the α-PVP and β-OH-α-PVP concentrations in oral fluid and urine, after snorting 10 mg or 20 mg of α-PVP. s12248-024-01012-7
α-PVP functions as a pure reuptake inhibitor at DAT and NET — it blocks transporter function without promoting monoamine release, distinguishing it mechanistically from amphetamine-type cathinonessupported
Comprehensive review of in vitro methods used to characterize cathinones at monoamine transporters, including uptake inhibition, release, voltage clamp, and Ca2+ mobilization assays. bs.apha.2023.09.001
The S-enantiomer is the pharmacologically active form, 10–20× more potent than the R-enantiomer at DAT and NETsupported
R-α-PVP was 10 to 20 times less potent at blocking dopamine and norepinephrine uptake. S-α-PVP is the active enantiomer responsible for most neurochemical, behavioral, and cardiovascular effects of the racemate. adb.12842
Serotonin transporter activity is negligible; none of 11 α-PVP analogs tested inhibited serotonin uptake at concentrations up to 10 µM.supported
None significantly inhibited SERT at 10 μM. All acted as DAT reuptake inhibitors with >1500-fold range of potency across analogs. acschemneuro.5b00160
Fatal cases overwhelmingly involve polydrug use — only 1.7% of Finnish synthetic cathinone fatalities involved α-PVP as the sole substancesupported
In only 1.7% were SCs the sole drug. j.forsciint.2024.112297
Direct organ toxicity includes mitochondrial impairment in skeletal muscle and brain tissue. α-PVP demonstrates among the highest reinforcing potency of any cathinone tested, with 100% acquisition of self-administration in ratspartially supported
α-PVP directly myotoxic to C2C12 myoblasts: impairs cell membrane integrity, depletes ATP, increases mitochondrial superoxide (50–2000 µM range). Inhibits mitochondrial complex I specifically. ijms20071561
Direct organ toxicity includes mitochondrial impairment in skeletal muscle and brain tissue. α-PVP demonstrates among the highest reinforcing potency of any cathinone tested, with 100% acquisition of self-administration in ratspartially supported
α-PVP (20 mg/kg) significantly impaired spatial learning/memory and brain mitochondrial function in Wistar rats; increased ROS, lipid peroxidation, collapsed MMP. j.taap.2023.116497
Direct organ toxicity includes mitochondrial impairment in skeletal muscle and brain tissue. α-PVP demonstrates among the highest reinforcing potency of any cathinone tested, with 100% acquisition of self-administration in ratspartially supported
Reinforcing effectiveness correlated with selectivity for DAT over SERT... rank order for selectivity at DAT over SERT: α-PVP > α-PPP > MDPV > MDPBP > MDPPP > cocaine. s41386-018-0209-3
history7 · 5 ok
Concurrently, reports of traffic accidents caused by α-PVP-impaired drivers emerged in Japan, prompting domestic regulatory action.supported
Caused traffic accidents in Japan. jts.42.539
Claim in history — not_supportednot supportedworking →
The specific date and laboratory of first synthesis have not been confirmed in the published literature, though the compound likely appears in early pyrovalerone analog patent series from that era. α-PVP constitutes one of two principal chemical scaffolds for the synthetic cathinone designer drug family, the other being the methcathinone scaffold.supported
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 (Flakka). ijms21218185
Detection in US clinical urine specimens began no later than February 2011, based on analysis of 34,561 specimens collected between 2011 and 2013supported
α-PVP (PVP) detected in US urine specimens (2011-2013) bku021
Claim in history — inconclusiveinconclusiveworking →
α-PVP attracted intense media attention in 2014–2015, particularly in Broward County, Florida, where bizarre behavioral incidents — erratic public behavior, violence, and agitated delirium — were attributed to its use under the street names "Flakka" and "Gravel"supported
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 (Flakka). ijms21218185
Following scheduling in major jurisdictions, α-PVP's structural scaffold became the basis for next-generation designer cathinones — halogenated and alkyl-modified analogs that continued to appear on drug markets. α-PVP itself remains prevalent in forensic casework; in Finland, it was detected in 118 post-mortem cases between 2018 and 2023, and it ranked among the most common novel psychoactive substances identified in Polish biological specimens during 2012–2014.supported
136 findings of α-PVP, α-PHP, or α-PiHP in 118 death cases in Finland (2018–2023). j.forsciint.2024.112297
receptor-pharmacology5 · 5 ok
The DAT/SERT selectivity ratio exceeds 4,030 as measured by fluorescent dye-based monoamine uptake assayssupported
α-PVP DAT/SERT inhibition ratio >4030. Used as reference compound for method validation. dta.3547
The pyrrolidine ring moiety combined with the pentyl alkyl chain confers optimal fit at the DAT binding pocket and maximum potency at both DAT and NET.supported
pyrrolidine moiety and long alkyl chain correlate with higher potency. fnins.2020.00009
Duart-Castells et al. reported Ki values at human DAT from binding assays, confirming high-affinity interaction consistent with the pyrrolidine ring's role in DAT pocket engagement.supported
Molecular docking and Ki values at hDAT reported. α-PVP characterized as potent DAT inhibitor with very low affinity for SERT; pyrrolidine ring increases potency vs methyl/ethyl amine substitutions. j.neuropharm.2021.108475
Multi-electrode array recordings revealed that high concentrations of α-PVP produced partially irreversible suppression of spontaneous neuronal network activity, suggesting neurotoxic potential at supratherapeutic exposuressupported
High concentrations produced partially irreversible inhibition of neuronal activity. fnins.2020.00009
In ex vivo rat brain synaptosome assays, S-α-PVP demonstrated 10–20× greater potency than R-α-PVP at both DAT and NETsupported
R-α-PVP was 10 to 20 times less potent at blocking dopamine and norepinephrine uptake. adb.12842
chemistry4 · 4 ok
The IUPAC name is 1-phenyl-2-pyrrolidin-1-ylpentan-1-one. α-PVP is structurally related to pyrovalerone (4'-methyl-α-PVP) and MDPV (3,4-methylenedioxy-α-PVP), differing from pyrovalerone by absence of the 4'-methyl ring substituent and from MDPV by absence of the 3,4-methylenedioxy group.supported
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 (Flakka). ijms21218185
The IUPAC name is 1-phenyl-2-pyrrolidin-1-ylpentan-1-one. α-PVP is structurally related to pyrovalerone (4'-methyl-α-PVP) and MDPV (3,4-methylenedioxy-α-PVP), differing from pyrovalerone by absence of the 4'-methyl ring substituent and from MDPV by absence of the 3,4-methylenedioxy group.supported
α-PVP is one of two principal chemical scaffolds for the synthetic cathinone family. bs.apha.2023.09.001
Structure-activity relationship studies confirm that the pyrrolidine ring and extended alkyl chain together confer highest DAT and NET potency — chain elongation and pyrrolidine bulk are the principal determinants of transporter binding affinity.supported
α-PVP inhibits monoamine uptake via hDAT and hNET at low micromolar concentrations; pyrrolidine moiety and long alkyl chain correlate with higher potency. fnins.2020.00009
R-α-PVP is at least 30× less potent than S-α-PVP in self-administration assays, confirming that the reinforcing properties of the racemate are attributable to the S-isomerpartially supported
R-α-PVP was 10 to 20 times less potent at blocking dopamine and norepinephrine uptake. S-α-PVP is the active enantiomer responsible for most neurochemical, behavioral, and cardiovascular effects of the racemate. adb.12842
comparative-pharmacology4 · 4 ok
Among pyrrolidine-containing cathinones, its DAT/SERT selectivity ratio (>4,030) is the highest characterized, exceeding MDPV and all other tested congeners.supported
α-PVP DAT/SERT inhibition ratio >4030. Used as reference compound for method validation. dta.3547
Reinforcing effectiveness rank order: α-PVP ≈ MDPBP > α-PPP > MDPPP, all exceeding cocainepartially supported
α-PVP approximately equal to MDPBP in reinforcing potency; rank order: α-PVP ≈ MDPBP > α-PPP > MDPPP. j.neuropharm.2017.08.018
α-PVP produces cocaine-like discriminative stimulus effects in rhesus monkeys, indicating qualitative similarity in subjective profilesupported
α-PVP produced dose- and time-dependent cocaine-like discriminative stimulus effects in rhesus monkeys. adb.12399
Both compounds elevate extracellular dopamine in the nucleus accumbens, but when co-administered at low doses, the α-PVP + MDPV mixture produces significantly greater locomotor activation than either compound alone, particularly in females.partially supported
MDPV analogs such as α-PVP display similar ability to inhibit DAT and increase extracellular dopamine concentrations. 7854_2016_53
clinical-evidence3 · 2 ok
Di Trana et al. characterized the pharmacokinetic disposition of α-PVP and its metabolites in urine and oral fluid following intranasal self-administration in 8 healthy volunteers at 10 mg and 20 mg doses, providing the only published human pharmacokinetic dataset.supported
An observational non-controlled naturalistic study on 8 healthy volunteers was conducted to assess the α-PVP and β-OH-α-PVP concentrations in oral fluid and urine, after snorting 10 mg or 20 mg of α-PVP. s12248-024-01012-7
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Analysis of 118 post-mortem Finnish cases (2018–2023) documented α-PVP blood concentrations and co-intoxicant profiles, with α-PVP implicated in the cause of death in 29% of positive casessupported
136 findings of α-PVP, α-PHP, or α-PiHP in 118 death cases in Finland (2018–2023). Median α-PVP femoral blood concentration in fatal poisonings: 0.18 mg/L (range 0.03–2.6 mg/L). 34 fatal poisonings (29%). Concomitant drugs in 69–92% of cases. j.forsciint.2024.112297
pharmacokinetic-detail2 · 1 ok
The only published human pharmacokinetic data derive from a naturalistic observational study of intranasal α-PVP administration in 8 healthy volunteers.supported
An observational non-controlled naturalistic study on 8 healthy volunteers was conducted to assess the α-PVP and β-OH-α-PVP concentrations in oral fluid and urine, after snorting 10 mg or 20 mg of α-PVP. s12248-024-01012-7
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
effects-overview1 · 1 ok
Relative to cocaine, α-PVP produces qualitatively similar but more potent dopaminergic stimulation — rhesus monkeys cannot distinguish the two in discrimination assayssupported
α-PVP produced dose- and time-dependent cocaine-like discriminative stimulus effects in rhesus monkeys. adb.12399