MDPV and α-PVP use in humans: The twisted sisters

Karila, Laurent; Lafaye, Geneviève; Scocard, Amandine; Cottencin, Olivier; Benyamina, Aminé

doi:10.1016/j.neuropharm.2017.10.007

Cited by 96 publications

(52 citation statements)

References 64 publications

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“…Finally, increasing levels of clinical concerns have been associated with the use of pyrovalerone‐like molecules , including α‐PVP and MDPV, whose clinical effects are individual, dose‐ and route of administration‐dependent . Palamar et al analysed data from a 2016/2017 large‐scale ( n = 3786) US study of high school senior subjects. Overall, 0.8% (95% CI: 0.5–1.2) of seniors was estimated to have used α‐PVP ( flakka ; zombie drug ) over the previous year.…”

Section: Resultsmentioning

confidence: 99%

“…Symptoms of high body temperature (3/8), tachycardia (5/8), hypertension (3/8), acid‐base balance disorder (5/8), coagulopathy (4/6), increased blood creatinine phosphokinase (6/8) and blood lactate levels (5/7) were observed. Use of flakka has been associated with at least 80 deaths in the USA . In a forensic setting, MDPV was detected in blood and urine samples of 50 individuals involved in violent crimes, including bodily harm, robberies, homicides and acts of resistance.…”

Section: Resultsmentioning

confidence: 99%

“…Conversely, Karila et al 68 Finally, increasing levels of clinical concerns have been associated with the use of pyrovalerone-like molecules, including α-PVP and MDPV, whose clinical effects are individual, dose-and route of administration-dependent. 71 Palamar et al 72 Umebachi et al 74 and blood lactate levels (5/7) were observed. Use of flakka has been associated with at least 80 deaths in the USA.…”

Section: Cathinone Categories; Clinical Peculiaritiesmentioning

confidence: 96%

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The clinical challenges of synthetic cathinones

Schifano

Napoletano

Arillotta

et al. 2020

Brit J Clinical Pharma

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Aims Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS‐related, online sources; and (ii) describe the associated acute/long term clinical scenario and the related treatment/management plan. Methods After about 18 months of operation and exclusion of false positives/duplicates, some 4204 unique NPS molecules were included in the NPSfinder® crawling/navigating software database. Most popular NPS included: 1265 psychedelic phenethylamines (30.1%; confidence interval [CI] 95%: 28.7–31.5%); 1253 synthetic cannabinoids (29.8%; CI 95%: 28.4–31.2%); 429 synthetic opioids (10.2%; CI 95%: 9.3–10.2%); and 171 synthetic cathinones (4.1%; CI 95% 3.5–4.7%). Conversely, the United Nations Office on Drugs and Crime and the European Monitoring Centre for Drugs and Drug Addiction databases respectively included 169 and 140 cathinones. Overall, the 3 databases reported some 222 synthetic cathinones, and 41 were uniquely identified by the NPSfinder®. Results In terms of clinical scenarios, synthetic cathinone ingestion is initially associated with stimulant effects; however, psychopathological disturbances, violence, suicidal behaviour, hyperthermia, coma and death have also been described. Conclusion The proportion of cathinones commented on by psychonaut fora appeared to be relatively small, and similar to those reported by both the United Nations Office on Drugs and Crime and European Monitoring Centre for Drugs and Drug Addiction. This may be associated with a recent significant decline in both cathinone‐related consumption and acute medical presentation. Due to their complex behavioural and medical toxicity issues, healthcare professionals should be, however, be educated to recognise the signs and symptoms of NPS, including synthetic cathinone, ingestion.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cathinone Categories; Clinical Peculiaritiesmentioning

confidence: 96%

See 1 more Smart Citation

The clinical challenges of synthetic cathinones

Schifano

Napoletano

Arillotta

et al. 2020

Brit J Clinical Pharma

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“…People who abuse synthetic cathinones commonly show violent and aggressive behavior, delusions, uncontrollable, bizarre, and intense paranoia, jerking muscle movements, delirious thoughts, and thoughts of violence from/towards others . Some users have reported mental and behavioral disorders, such as hallucinating that people were hiding in walls, swimming toward a snow bank to hide from snipers, and breaking into a police station to seek safety . It is worth noting that α‐pyrrolidinovalerophenone (α‐PVP), one of the “second generation” of pyrrolidinophenones that belongs to the group of synthetic cathinones, has been found to be related to more cases of self‐injury, aggressive behavior, and suicidal ideations reported by emergency department staff and first responders .…”

Section: Introductionmentioning

confidence: 99%

Determination of synthetic cathinone α‐pyrrolidinovalero‐phenone and its metabolite in urine using solid‐phase extraction and gas chromatography–mass spectrometry

Cheng

Hsieh

Chen

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale The presence of α‐pyrrolidinovalerophenone (α‐PVP) and its metabolites in urine is evidence of the administration of α‐PVP. A toxicological challenge is that the metabolites of α‐PVP exhibit amphoteric properties, which make them unsuitable for detection using gas chromatography–mass spectrometry (GC/MS). In the study reported, proper derivatization and sample extraction were essential for improving the sensitivity for GC/MS analysis. Methods An automated solid‐phase extraction (SPE) method has been developed and optimized. The derivatization efficiency was tested using longer reaction time and the addition of polar pyridine into a mixture of N,O‐bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane. Method validation, including linearity, limit of detection, precision, accuracy, and recovery, was evaluated using automatic SPE and GC/MS. Results The results suggested that adding pyridine to BSTFA (1:1, v/v) significantly improved derivatization efficiency and precision. After optimization, the linear range was from 25 to 1000 ng mL−1 with R2 > 0.9950. The limit of detection was 5 ng mL−1 for α‐PVP and 25 ng mL−1 for OH‐α‐PVP. The recovery for SPE was over 88%. The inter‐day and intra‐day precisions were less than 15%. A forensic sample has been found containing α‐PVP (67.3 ng mL−1) and OH‐α‐PVP (560.2 ng mL−1). Conclusions This study is the first to validate an auto‐SPE‐GC/MS method for the quantification and qualification of α‐PVP and OH‐α‐PVP in urine. We have successfully improved the derivatization efficiency and developed a sensitive and semi‐automatic approach. This approach is desirable for the detection of synthetic cathinone at trace levels in biological samples.

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“…Synthetic cathinones (SCs), exemplified by the schedule 1 drugs 4‐methyl‐ N ‐methylcathinone (mephedrone), α‐pyrrolidinopentiophenone (α‐PVP), and methylenedioxypyrovalerone (MDPV), are β‐keto analogs of amphetamines. They are powerful psychostimulants that produce effects similar to other illicit drugs, including cocaine, 3,4‐methylenedioxymethamphetamine (MDMA), and methamphetamine . Like amphetamine, the cathinone scaffold is amenable to several, slight, chemical modifications that permit the synthesis of numerous, unique SCs that retain psychoactive properties.…”

Section: Introductionmentioning

confidence: 99%

The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT_2A receptors: In vitro and in vivo evidence

Chen

Blough

Murnane

et al. 2019

Drug Testing and Analysis

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Synthetic cathinones (SCs) are β‐keto analogs of amphetamines. Like amphetamines, SCs target monoamine transporters; however, unusual neuropsychiatric symptoms have been associated with abuse of some SCs, suggesting SCs might possess additional pharmacological properties. We performed radioligand competition binding assays to assess the affinities of nine SCs at human 5‐HT2A receptors (5‐HT2AR) and muscarinic M1 receptors (M1R) transiently expressed in HEK293 cells. None of the SCs exhibited affinity at M1R (minimal displacement of [~Kd] [3H]scopolamine up to 10 μM). However, two SCs, α‐pyrrolidinopropiophenone (α‐PPP) and 4‐methyl‐α‐PPP, had low μM Ki values at 5‐HT2AR. In 5‐HT2AR–phosphoinositide hydrolysis assays, α‐PPP and 4‐methyl‐α‐PPP displayed inverse agonist activity. We further assessed the 5‐HT2AR functional activity of α‐PPP, and observed it competitively antagonized 5‐HT2AR signaling stimulated by the 5‐HT2R agonist (±)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI; Kb = 851 nM). To assess in vivo 5‐HT2AR activity, we examined the effects of α‐PPP on the DOI‐elicited head‐twitch response (HTR) in mice. α‐PPP dose‐dependently blocked the HTR with maximal suppression at 10 mg/kg (P < 0.0001), which is a moderate dose used in studies investigating psychostimulant properties of α‐PPP. To corroborate a 5‐HT2AR mechanism, we also tested 3,4‐methylenedioxy‐α‐PPP (MDPPP) and 3‐bromomethcathinone (3‐BMC), SCs that we observed had 5‐HT2AR Kis > 10 μM. Neither MDPPP nor 3‐BMC, at 10 mg/kg doses, attenuated the DOI HTR. Our results suggest α‐PPP has antagonist interactions at 5‐HT2AR in vitro that may translate at physiologically‐relevant doses in vivo. Considering 5‐HT2AR antagonism has been shown to mitigate effects of psychostimulants, this property may contribute to α‐PPPs unpopularity compared to other monoamine transporter inhibitors.

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MDPV and α-PVP use in humans: The twisted sisters

Cited by 96 publications

References 64 publications

The clinical challenges of synthetic cathinones

The clinical challenges of synthetic cathinones

Determination of synthetic cathinone α‐pyrrolidinovalero‐phenone and its metabolite in urine using solid‐phase extraction and gas chromatography–mass spectrometry

The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT_2A receptors: In vitro and in vivo evidence

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MDPV and α-PVP use in humans: The twisted sisters

Cited by 96 publications

References 64 publications

The clinical challenges of synthetic cathinones

The clinical challenges of synthetic cathinones

Determination of synthetic cathinone α‐pyrrolidinovalero‐phenone and its metabolite in urine using solid‐phase extraction and gas chromatography–mass spectrometry

The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT2A receptors: In vitro and in vivo evidence

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The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT_2A receptors: In vitro and in vivo evidence