MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations

Diestelmann, Marco; Zangl, Anna; Herrle, Inge; Koch, Eva; Graw, Matthias; Paul, Liane D.

doi:10.1016/j.forsciint.2017.12.003

Cited by 41 publications

(12 citation statements)

References 33 publications

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“…In many cases, subjects showed highly aggressive and violent behaviour; the risk for such behaviours increased with MDPV plasma concentrations above 30 mg/L . According to Szily and Bitter, in Hungary there has been an increasing number of hospitalized patients with acute psychosis using MDPV. Finally, Dzhuvalyakov et al collected postmortem samples taken from 13 pyrrolidinovalerophenone poisoning victims from the Astrakhan region; they identified signs of chronic intoxication, which manifested themselves in the form of mixed gliosis and various lesions of brain neurons.…”

Section: Resultsmentioning

confidence: 99%

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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%

“…In many cases, subjects showed highly aggressive and violent behaviour; the risk for such behaviours increased with MDPV plasma concentrations above 30 mg/L. 75 According to Szily and Bitter, 76 in Hungary there has been an increasing number of hos-…”

Section: Cathinone Categories; Clinical Peculiaritiesmentioning

confidence: 99%

The clinical challenges of synthetic cathinones

Schifano

Napoletano

Arillotta

et al. 2020

Brit J Clinical Pharma

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“…1 Synthetic cathinones are a major category of NPS that cause psychomotor stimulant effects in humans and laboratory animals. [4][5][6][7][8][9] As such, these substances represent a serious risk to public health. After high-dose administration or repeated use, synthetic cathinones can produce serious medical complications including tachycardia, hypertension, agitation, psychosis, aggressive behavior, seizures, and in some cases, death.…”

Section: Introductionmentioning

confidence: 99%

“…After high-dose administration or repeated use, synthetic cathinones can produce serious medical complications including tachycardia, hypertension, agitation, psychosis, aggressive behavior, seizures, and in some cases, death. [4][5][6][7][8][9] As such, these substances represent a serious risk to public health.…”

Section: Introductionmentioning

confidence: 99%

Analytical quantification, intoxication case series, and pharmacological mechanism of action for N‐ethylnorpentylone (N‐ethylpentylone or ephylone)

Costa

Cunha

Lanaro

et al. 2018

Drug Testing and Analysis

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Synthetic cathinones continue to proliferate in clandestine drug markets worldwide. N-ethylnorpentylone (also known as N-ethylpentylone or ephylone) is a popular emergent cathinone, yet little information is available about its toxicology and pharmacology. Here we characterize the analytical quantification, clinical presentation, and pharmacological mechanism of action for N-ethylnorpentylone. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify N-ethylnorpentylone in blood obtained from human cases. Clinical features exhibited by the intoxicated individuals are described. The activity of N-ethylnorpentylone at plasma membrane transporters for dopamine (DAT), norepinephrine (NET) and 5-HT (SERT) was assessed using in vitro assays measuring uptake inhibition and evoked release of [ H] neurotransmitters in rat brain synaptosomes. Our LC-MS/MS method assayed N-ethylnorpentylone concentrations with limits of detection and quantification of 1 and 5 ng/mL, respectively. Quantitation was linear from 5 to 500 ng/mL, and the method displayed specificity and reproducibility. Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death. N-Ethylnorpentylone was a potent inhibitor at DAT (IC = 37 nM), NET (IC = 105 nM) and SERT (IC = 383 nM) but displayed no transporter releasing activity. We present a validated method for quantifying N-ethylnorpentylone in human case work. The drug is a psychomotor stimulant capable of inducing serious cardiovascular and neurological side-effects which can be fatal. In vitro findings indicate that N-ethylnorpentylone exerts its effects by potent blockade of DAT and NET, thereby elevating extracellular levels of dopamine and norepinephrine in the brain and periphery.

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“…In addition to the euphorigenic effects, a considerable number of clinical case reports indicate that MDPV intoxication is associated with adverse behavioral and physiological effects (White, 2016) (Beck et al, 2015; Elliott and Evans, 2014; Spiller et al, 2011; Vallersnes et al, 2016). In reports confirming MDPV in either urine or serum, the adverse effects include agitation, tachycardia, hallucinations, delirium, hyperthermia and rhabdomyolysis (Beck et al, 2015; Spiller et al, 2011), psychosis (Vallersnes et al, 2016), suicidal ideation (Elliott and Evans, 2014), and aggressive behavior (Diestelmann et al, 2018). As occurs with chronic use of intoxicating doses of other potent stimulants (American Psychiatric Association.…”

Section: Introductionmentioning

confidence: 99%

Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone

et al. 2018

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Among cathinone drugs known as bath salts, methylenedioxypyrovalerone (MDPV) exerts its potent actions via the dopamine (DA) system, and at intoxicating doses may produce adverse behavioral effects. Previous work by our group suggests that prolonged alterations in correlated neural activity between cortical and striatal areas could underlie, at least in part, the adverse reactions to this bath salt drug. In the present study, we assessed the effect of acute MDPV administration on brain functional connectivity at 1 and 24 h in rats. Using graph theory metrics to assess in vivo brain functional network organization we observed that 24 h after MDPV administration there was an increased clustering coefficient, rich club index, and average path length. Increases in these metrics suggests that MDPV produces a prolonged pattern of correlated activity characterized by greater interactions between subsets of high degree nodes but a reduced interaction with regions outside this core subset. Further analysis revealed that the core set of nodes include prefrontal cortical, amygdala, hypothalamic, somatosensory and striatal areas. At the molecular level, MDPV downregulated the dopamine transporter (DAT) in striatum and produced a shift in its subcellular distribution, an effect likely to involve rapid internalization at the membrane. These new findings suggest that potent binding of MDPV to DAT may trigger internalization and a prolonged alteration in homeostatic regulation of DA and functional brain network reorganization. We propose that the observed MDPV-induced network reorganization and DAergic changes may contribute to previously reported adverse behavioral responses to MDPV.

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MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations

Cited by 41 publications

References 33 publications

The clinical challenges of synthetic cathinones

The clinical challenges of synthetic cathinones

Analytical quantification, intoxication case series, and pharmacological mechanism of action for N‐ethylnorpentylone (N‐ethylpentylone or ephylone)

Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone

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