Sudden death after sustained restraint following self-administration of the designer drug α-pyrrolidinovalerophenone

Nagai, Hisashi; Saka, Kanju; Nakajima, Makoto; Maeda, Hidyuki; Kuroda, Ryo; Igarashi, Atsuko; Tsujimura-Ito, Takako; Nara, Akina; Komori, Masatomo; Yoshida, Ken

doi:10.1016/j.ijcard.2013.12.262

Cited by 93 publications

(26 citation statements)

References 9 publications

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“…Recently a case of neonatal withdrawal syndrome, with increased jitteriness, irritability, high pitched cry, hypertonia in the limbs, and brisk tendon reflexes, after chronic maternal consumption of 4-MEC has been reported (Pichini et al, 2014). There were more M a n u s c r i p t 15 than one hundred analytically confirmed fatal cases involving α-PVP (EMCDDA, 2015c;Nagai et al, 2014;Gil et al, 2015;Potocka-Banaś et al, 2015;Sykutera et al, 2015). Legal status of 4-MEC, 4-MePPP, and α-PVP is given in Table 2.…”

Section: Synthetic Cathinonesmentioning

confidence: 99%

Next generation of novel psychoactive substances on the horizon – A complex problem to face

Zawilska

Andrzejczak

2015

Drug and Alcohol Dependence

166

123

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Section: Synthetic Cathinonesmentioning

confidence: 99%

Next generation of novel psychoactive substances on the horizon – A complex problem to face

Zawilska

Andrzejczak

2015

Drug and Alcohol Dependence

166

123

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“…These observations suggest that this group of synthetic cathinones is particularly dangerous to human life (EMCDDA 2014(EMCDDA , 2015aHasegawa et al 2014;Kudo et al 2015;Nagai et al 2014). In contrast to numerous case reports of intoxications with pyrovalerone cathinones, limited data exist on the in vitro cytotoxicity of these compounds.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Activity of Pyrovalerone Derivatives, an Emerging Group of Psychostimulant Designer Cathinones

et al. 2016

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The growing popularity of novel psychoactive substances (NPS) has aroused the concerns of public health specialists. The pyrovalerone derivatives are a branch of synthetic cathinones, a very popular group of psychostimulant NPS. Despite numerous case reports of fatal intoxications, little is known about the cytotoxicity of these substances. Therefore, this study was aimed to evaluate the toxic properties of pyrovalerone, its highly prevalent derivative 3,4-methylenedioxypyrovalerone (3,4-MDPV) with its two major metabolites (catechol-MDPV and methylcatechol-MDPV) and the structural isomer 2,3-MDPV, together with newer members of the group, i.e., α-pyrrolidinovalerothiophenone (α-PVT) and α-pyrrolidinooctanophenone (PV9), using model human cell lines for neurons (SH-SY5Y), hepatocytes (Hep G2), and upper airway epithelium (RPMI 2650). We found that the first generation pyrovalerones (pyrovalerone, 3,4-MDPV, and 2,3-MDPV) produced a modest decrease of mitochondrial activity in the three examined cell lines, but were active in lower concentrations than methamphetamine used as a reference psychostimulant compound. Since catechol-MDPV displayed greater toxic potential than the parent compound, we suggest that the toxicity of 3,4-MDPV could be attributed to activity of this metabolite. Strikingly, the two new generation pyrovalerones, α-PVT and PV9, seem to be the most potent cytotoxic compounds: both induced highly pronounced mitochondrial dysfunction; the latter also demonstrated significant damage to cell membranes. The reported in vitro toxic activity of pyrovalerone cathinones against different cell types reinforces existing concerns regarding the health risks associated with the intake of these drugs.

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“…In Electronic supplementary material The online version of this article (doi:10.1007/s00216-015-8763-6) contains supplementary material, which is available to authorized users. spite of their recent introduction, deaths associated with the use of these NPS were already reported [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

In vitro Phase I and Phase II metabolism of α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol

et al. 2015

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The aim of the present study was to identify the in vitro Phase I and Phase II metabolites of three new psychoactive substances: α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV), and methedrone, using human liver microsomes and human liver cytosol. Accurate-mass spectra of metabolites were obtained using liquid chromatography-quadrupole time-of-flight mass spectrometry. Six Phase I metabolites of α-PVP were identified, which were formed involving reduction, hydroxylation, and pyrrolidine ring opening reactions. The lactam compound was the major metabolite observed for α-PVP. Two glucuronidated metabolites of α-PVP, not reported in previous in vitro studies, were further identified. MDPV was transformed into 10 Phase I metabolites involving reduction, hydroxylation, and loss of the pyrrolidine ring. Also, six glucuronidated and two sulphated metabolites were detected. The major metabolite of MDPV was the catechol metabolite. Methedrone was transformed into five Phase I metabolites, involving N- and O-demethylation, hydroxylation, and reduction of the ketone group. Three metabolites of methedrone are reported for the first time. In addition, the contribution of individual human CYP enzymes in the formation of the detected metabolites was investigated.

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Sudden death after sustained restraint following self-administration of the designer drug α-pyrrolidinovalerophenone

Cited by 93 publications

References 9 publications

Next generation of novel psychoactive substances on the horizon – A complex problem to face

Next generation of novel psychoactive substances on the horizon – A complex problem to face

Cytotoxic Activity of Pyrovalerone Derivatives, an Emerging Group of Psychostimulant Designer Cathinones

In vitro Phase I and Phase II metabolism of α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol

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