A review of synthetic cathinones emerging in recent years (2019–2022)

Kuropka, Patryk; Zawadzki, Marcin; Szpot, Paweł

doi:10.1007/s11419-022-00639-5

Cited by 24 publications

(21 citation statements)

References 130 publications

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“…Besides elucidation of the endogenous response, urine also offers the possibility to analyze for drug metabolites. The knowledge about xenobiotic metabolic pathways is essential for clinical and forensic toxicology to develop suitable analytical screening procedures to detect consumption [5,8,9]. Compared to conventional methods for analyzing metabolic pathways, an untargeted urinary toxicometabolomics approach allows for the detection of metabolites which might be overlooked as they are not expected [3,14,35].…”

Section: Methodsmentioning

confidence: 99%

“…Between 2019 and 2022, 29 synthetic cathinones have been identified for the first time [5]. They are classified as stimulants or amphetamine-type stimulants [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…In preclinical studies, two ways on interaction with monoamine transporters were demonstrated: monoamine transporter blockers such as cocaine or monoamine transporter substrates stimulated the release of neurotransmitters such as amphetamine and MDMA [8,9]. The synthetic cathinone PCYP (2-cyclohexyl-1-phenyl-2-pyrrolidin-1-yl-ethan-1-one) was first detected in March 2019 in the U.S., and in Europe the first case report was published 2020 [5]. Due to the presence of the lipophilic and bulky cyclohexyl ring, PCYP exhibited an up to twofold stronger interaction with dopamine transporters in vitro compared to alpha-pyrrolidinovalerophenone (α-PVP).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, it shows stronger dopaminergic stimulation and higher addictive potential [10]. This biochemical reaction led to desired effects such as stimulation and euphoria, but also to adverse effects including restlessness, anxiety, psychosis, tachycardia, and hyperthermia [5]. So far, no data are available about the metabolic fate of PCYP and the impact of PCYP on endogenous metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%

“…To date, only one case report of PCYP intake in Europe has been published [5]. It cannot be excluded that there is, was, and will be more extensive distribution.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS

Hemmer

Wagmann

Pulver³

et al. 2022

Metabolites

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Synthetic cathinones are one important group amongst new psychoactive substances (NPS) and limited information is available regarding their toxicokinetics and -dynamics. Over the past few years, nontargeted toxicometabolomics has been increasingly used to study compound-related effects of NPS to identify important exogenous and endogenous biomarkers. In this study, the effects of the synthetic cathinone PCYP (2-cyclohexyl-1-phenyl-2-(1-pyrrolidinyl)-ethanone) on in vitro and in vivo metabolomes were investigated. Pooled human-liver microsomes and blood and urine of male Wistar rats were used to generate in vitro and in vivo data, respectively. Samples were analyzed by liquid chromatography and high-resolution mass spectrometry using an untargeted metabolomics workflow. Statistical evaluation was performed using univariate and multivariate statistics. In total, sixteen phase I and one phase II metabolite of PCYP could be identified as exogenous biomarkers. Five endogenous biomarkers (e.g., adenosine and metabolites of tryptophan metabolism) related to PCYP intake could be identified in rat samples. The present data on the exogenous biomarker of PCYP are crucial for setting up analytical screening procedures. The data on the endogenous biomarker are important for further studies to better understand the physiological changes associated with cathinone abuse but may also serve in the future as additional markers for an intake.

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Section: Methodsmentioning

confidence: 99%

“…Between 2019 and 2022, 29 synthetic cathinones have been identified for the first time [5]. They are classified as stimulants or amphetamine-type stimulants [6,7].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…To date, only one case report of PCYP intake in Europe has been published [5]. It cannot be excluded that there is, was, and will be more extensive distribution.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS

Hemmer

Wagmann

Pulver³

et al. 2022

Metabolites

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Pharmacological profile, phase I metabolism, and excretion time profile of the new synthetic cathinone 3,4‐Pr‐PipVP

Schwelm

Persson

Pulver

et al. 2023

Drug Testing and Analysis

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Abstract1‐(2,3‐Dihydro‐1H‐inden‐5‐yl)‐2‐(piperidin‐1‐yl)pentan‐1‐one (3,4‐Pr‐PipVP), a novel synthetic cathinone (SCat), was first identified in 2022 in Germany. The product was marketed as 1‐(bicyclo[4.2.0]octa‐1,3,5‐trien‐3‐yl)‐2‐(pyrrolidin‐1‐yl)pentan‐1‐one (3,4‐EtPV), a substance not covered by the German New Psychoactive Substances Act (NpSG). Although originally intended to be an exploratory new synthetic cathinone containing the novel bicyclo[4.2.0]octatrienyl function, the compound was subsequently confirmed to contain an indanyl ring system scheduled under generic legislation like the NpSG. However, it is one of only a few marketed SCats carrying a piperidine ring. Inhibition experiments involving norepinephrine, dopamine, and serotonin transporters showed that 3,4‐Pr‐PipVP was a low potency blocker at all three monoamine transporters compared to related substances such as MDPV. Additionally, pharmacokinetic data were collected from pooled human liver microsomes incubations and from the analysis of authentic urine samples received after oral administration of 5 mg 3,4‐Pr‐PipVP hydrochloride. Phase I metabolites were tentatively identified in vitro and in vivo using liquid chromatography−time‐of‐flight mass spectrometry. Main metabolites were formed by metabolic reduction of the carbonyl function with and without additional hydroxylations at the propylene bridge of the molecule. Keto‐reduced H2–3,4‐Pr‐PipVP and H2‐piperidine‐OH‐3,4‐Pr‐PipVP as well as aryl‐OH‐3,4‐Pr‐PipVP, and indanyl‐OH‐piperidine‐OH‐3,4‐Pr‐PipVP are suggested as most suitable biomarkers for the detection of 3,4‐Pr‐PipVP since they were detected for much longer than the parent compound. 3,4‐Pr‐PipVP could be detected for up to 21 h whereas its metabolites were detectable for up to about 4 days.

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A narrative review of the neuropharmacology of synthetic cathinones—Popular alternatives to classical drugs of abuse

Kuropka¹,

Zawadzki

Szpot

2023

Human Psychopharmacology

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Objective To review the literature on the neuropharmacology of synthetic cathinones. Methods A comprehensive literature search was carried out across multiple databases (mainly PubMed, World Wide Web, and Google Scholar) using relevant keywords. Results Cathinones exhibit a broad toxicological profile, mimicking the effects of a wide variety of ‘classic drugs’ such as 3,4‐methylenedioxymethamphetamine (MDMA), methamphetamine and cocaine. Even small structural changes affect their interactions with key proteins. This article reviews existing knowledge of the mechanisms of action of cathinones at the molecular level, and key findings from research on their structure‐activity relationship. The cathinones are also classified according to their chemical structure and neuropharmacological profiles. Conclusions Synthetic cathinones represent one of the most numerous and widespread groups among new psychoactive substances. Initially developed for therapeutic purposes, they quickly started to be used recreationally. With a rapidly increasing number of new agents entering the market, structure‐activity relationship studies are valuable for assessing and predicting the addictive potential and toxicity of new and potential future substances. The neuropharmacological properties of synthetic cathinones are still not fully understood. A full elucidation of the role of some key proteins, including organic cation transporters, requires detailed studies.

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A review of synthetic cathinones emerging in recent years (2019–2022)

Cited by 24 publications

References 130 publications

In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS

In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS

Pharmacological profile, phase I metabolism, and excretion time profile of the new synthetic cathinone 3,4‐Pr‐PipVP

A narrative review of the neuropharmacology of synthetic cathinones—Popular alternatives to classical drugs of abuse

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