The expression of methiopropamine-induced locomotor sensitization requires dopamine D2, but not D1, receptor activation in the rat

Yoon, Hyung Shin; Cai, Wen Ting; Lee, Young Hun; Park, Kyung Tae; Lee, Yong Sup; Kim, Jeong-Hoon

doi:10.1016/j.bbr.2016.05.060

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…Behavioural studies show that chronic treatment with MPA does not significantly alter body weight growth and food intake in the mice, thermoregulation, muscle strength and motor activity on the accelerod, highlighting their apparent good health. The lack of facilitation on motor activity in the accelerod test is apparently in contrast with a previous study showing that repeated administration of MPA produces locomotor sensitization in rats, similar to other psychomotor stimulants [9]. The ineffectiveness of MPA in our study could be because mice are well trained in the accelerod test before the experimental section and they remain on the rotating rod for the whole acceleration time (i.e., 5 min).…”

Section: Discussioncontrasting

confidence: 99%

“…To the best of our knowledge, the literature contains no data on health hazards secondary to chronic MPA consumption, and no experimental studies evaluating its chronic toxicity have been performed. In light of recent scientific evidence highlighting the risk of addiction-like behaviour induced by MPA consumption [9], we evaluated the effects of chronic MPA abuse on body tissues, using a mouse model. Moreover, to better understand the effects of the chronic MPA treatment on mice behaviour, we investigated the effects of chronic MPA on mouse body weight changes and food intake, body temperature, muscle strength and motor coordination.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic effects of chronic and acute use of methiopropamine in a mouse model

et al. 2018

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Methiopropamine (MPA) is a structural analogue of methamphetamine and belongs to the category of the novel psychoactive substances. To the best of our knowledge, no experimental study has been performed to evaluate the organ damage evoked by MPA administration in an animal model. Therefore, the main purpose of the present study was to investigate the histological changes in CD-1 male mice following the chronic administration of MPA. MPA-chronically treated mice showed myocardial damage with features consistent with repeated episodes of ischemia and a pattern of kidney damage and gastrointestinal ischemia, with ischemic-necrotic lesions of variable extent. In agreement with the analogies between MPA and methamphetamine, we link organ damage secondary to MPA administration to the vasoconstrictive effect exhibited by both compounds. Chronically MPA-treated mice did not show changes in body weight, food intake, thermoregulation, muscular strength and motor coordination in the accelerod test. However, acute MPA administration significantly increased their heart rate and promoted vasoconstriction, which were associated with the sudden death of a subset of animals (40% of all chronically treated mice). In conclusion, the present study demonstrates that MPA consumption could induce health hazards, highlighting the risk of sudden catastrophic events; therefore, clinicians should be aware of these data and consider MPA screening when no other drug is identified by a urine drug screen.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phenotypic effects of chronic and acute use of methiopropamine in a mouse model

et al. 2018

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“…Psychedelics and hallucinogen determine alterations in the perception, beside mood and cognition modifications [ 157 ]. Within this class, tryptamines, e.g., N,N-dimethyltryptamine (DMT) and psilocybin, and “psychedelic amphetamines,” e.g., 2,5-dimethoxy-4-iodoamphetamine (DOI) and N-benzylphenethylamines (NBOMes), are included [ 7 , 158 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Giorgetti

Pascali

Fais

et al. 2021

Life

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Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.

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“…Despite MPA’s toxicological properties and growing diffusion, only a few countries have enacted legislation covering its abuse: Florida and Ohio in the United States, Belarus, China, Denmark, Estonia, Germany, Hungary, Portugal, Slovenia, Sweden, Turkey, and Switzerland. MPA is under a temporary drug classification in the United Kingdom 20,34 . Previous studies have outlined the phase I and phase II metabolism of MPA in both human and animal models, such as rats 20,35 .…”

Section: Introductionmentioning

confidence: 99%

“…MPA is under a temporary drug classification in the United Kingdom. 20,34 Previous studies have outlined the phase I and phase II metabolism of MPA in both human and animal models, such as rats. 20,35 Nonetheless, to the best of our knowledge, no information is yet available on the urinary excretion profile of MPA and its metabolites.…”

mentioning

confidence: 99%

Urinary excretion profile of methiopropamine in mice following intraperitoneal administration: A liquid chromatography–tandem mass spectrometry investigation

Camuto

Pellegrini

De-Giorgio

et al. 2020

Drug Testing and Analysis

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We have considered the urinary excretion profile of methiopropamine (MPA), a thiophene ring-based structural analog of methamphetamine with similar stimulant effects, with the aim of selecting the most appropriate marker(s) of intake that may be useful in forensic analysis. For this purpose, in vitro studies were preliminarily performed on human liver microsomes for tracing the phase I metabolic pathways of MPA, preselecting the best candidates as potential target analytes, and designing the optimal experimental strategy. In vivo studies were then conducted on mice, after the intraperitoneal administration of a 10-mg/kg dose. Urine samples were collected every 3 h in the first 9 h and, subsequently, from 24 to 36 h, and stored at-80 C until further analysis. The measurements were performed using a targeted procedure based on liquid/liquid extraction followed by liquid chromatography-tandem mass spectrometry analysis. Our results show that in the time interval 0-9 h after administration, MPA was extensively oxidized mainly to nor-MPA, oxo-MPA, and two hydroxylated metabolites (ie, hydroxy-aryl-methiopropamine and hydroxy-alkylmethiopropamine). All phase I metabolites underwent phase II metabolism, with the formation of nor-hydroxy-methiopropamine only in phase II, confirmed by the results obtained after enzymatic hydrolysis with β-glucuronidase and arylsulfatase. In the time interval 24-36 h after administration, only unchanged MPA and nor-MPA were detected, suggesting that these two markers are those endowed with the highest diagnostic value. The method was validated for these two principal markers, proving to be fit for anti-doping, toxicological, and forensic analyses.

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The expression of methiopropamine-induced locomotor sensitization requires dopamine D2, but not D1, receptor activation in the rat

Cited by 12 publications

References 26 publications

Phenotypic effects of chronic and acute use of methiopropamine in a mouse model

Phenotypic effects of chronic and acute use of methiopropamine in a mouse model

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Urinary excretion profile of methiopropamine in mice following intraperitoneal administration: A liquid chromatography–tandem mass spectrometry investigation

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