A mixed MDPV and benzodiazepine intoxication in a chronic drug abuser: Determination of MDPV metabolites by LC–HRMS and discussion of the case

Bertol, Elisabetta; Mari, Francesco; R, Berto; Mannaioni, Guido; Vaiano, Fabio; Favretto, Donata

doi:10.1016/j.forsciint.2014.08.002

Cited by 28 publications

(16 citation statements)

References 31 publications

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“…S2) was in agreement with previously published data [12,20,21,28]. The following paragraphs describe the identified metabolites in detail (Table 2 and This metabolite was observed in human urine [21,33] but not in studies investigating the in vitro human metabolism of MDPV [21].…”

Section: Mdpvsupporting

confidence: 90%

“…M2 was the major metabolite of MDPV, which was consistent with previous in vitro [20] and in vivo [21,33] [21].…”

Section: Mdpvsupporting

confidence: 90%

“…Meyer et al [21] found another metabolite in human urine with the same exact mass as M8 but with a totally different fragmentation pattern corresponding to the demethylenyl-methyl-hydroxy-alkyl-MDPV. Bertol et al [33] assigned the same metabolite, also in human urine, following the proposal of Meyer et al [21], but the MS/MS spectrum was not presented. Therefore, careful evaluation of the MS/MS spectrum and proper interpretation of the product ions is very important to reliably identify the structure of the metabolites.…”

Section: Mdpvmentioning

confidence: 99%

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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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Section: Mdpvsupporting

confidence: 90%

“…M2 was the major metabolite of MDPV, which was consistent with previous in vitro [20] and in vivo [21,33] [21].…”

Section: Mdpvsupporting

confidence: 90%

Section: Mdpvmentioning

confidence: 99%

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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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“…Because these agents act via a different mechanism not involving monoaminergic transmission, this may be a target that could receive less attention. As GABAergic neurons modulate cortical synchrony (Fries, 2009) and loss of synchrony can occur in psychosis (Moran and Hong, 2011), GABA-mediated rescue of functional connectivity in the regions reported here (prelimbic cortex, insular cortex, NAc) may be of clinical interest (Bertol et al, 2014;Stoica and Felthous, 2013). Additionally, although not considered here, the reduction in resting state functional connectivity could represent a functional signature associated with neurodegenerative effects that have been reported with other stimulant drugs (Blum et al, 2013;Gold et al, 2009).…”

Section: Discussionmentioning

confidence: 71%

“…While one candidate mechanism might involve MDPV effects via NET (Simmler et al, 2012), an additional and unexplored possibility, based on some clinical reports, is a mechanism indirectly involving γ-aminobutyric acid (GABA). Anxiolytic agents acting through GABA A , such as benzodiazepines (diazepam, lorazepam) and valproate, have proven effective in ameliorating the negative symptoms of bath salt intoxication (Bertol et al, 2014;Stoica and Felthous, 2013). Because these agents act via a different mechanism not involving monoaminergic transmission, this may be a target that could receive less attention.…”

Section: Discussionmentioning

confidence: 99%

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Colon-Perez

Tran

Thompson

et al. 2016

Neuropsychopharmacol

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The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D 1 /D 2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.

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Intended and unintended use of cathinone mixtures

Guirguis

Corkery

Stair

et al. 2017

Human Psychopharmacology

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Introduction Cathinones are one of the most popular categories of new psychoactive substances (NPS) consumed. Cathinones have different pharmacological activities and receptor selectivity for monoamine transporters based on their chemical structures. They are incorporated into NPS mixtures and used with other NPS or ‘traditional’ drugs. Cathinone use represents significant health risks to individuals and is a public health burden. Methods Evidence of poly‐NPS use with cathinones, seizure information, and literature analyses results on NPS mixtures was systematically gathered from online database sources, including Google Scholar, Scopus, Bluelight, and Drugs‐Forum. Results and discussion Results highlight the prevalence of NPS with low purity, incorporation of cathinones into NPS mixtures since 2008, and multiple members of the cathinone family being present in individual UK‐seized samples. Cathinones were identified as adulterants in NPS marketed as being pure NPS, drugs of abuse, branded products, herbal blends, and products labelled “not for human consumption.” Toxicity resulting from cathinone mixtures is unpredictable because key attributes remain largely unknown. Symptoms of intoxication include neuro‐psychological, psychiatric, and metabolic symptoms. Proposed treatment includes holistic approaches involving psychosocial, psychiatric and pharmacological interventions. Conclusion Raising awareness of NPS, education, and training of health care professionals are paramount in reducing harms related to cathinone use.

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A mixed MDPV and benzodiazepine intoxication in a chronic drug abuser: Determination of MDPV metabolites by LC–HRMS and discussion of the case

Cited by 28 publications

References 31 publications

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

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

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Intended and unintended use of cathinone mixtures

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