Methiopropamine and its acute behavioral effects in mice: is there a gray zone in new psychoactive substances users?

De-Giorgio, Fabio; Bilel, Sabrine; Tirri, Micaela; Arfè, Raffaella; Trapella, Claudio; Camuto, Cristian; Foti, Federica; Frisoni, Paolo; Neri, Margherita; Botrè, Francesco; Marti, Matteo

doi:10.1007/s00414-020-02302-3

Cited by 20 publications

(19 citation statements)

References 103 publications

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“…Moreover, PMA shows a biphasic effect at the highest dose tested, which cannot be directly attributed to its hallucinogenic action. Yet, the increase in tactile response, as for MPA [ 27 ], could be related to its facilitation of DA and NE [ 51 ] release.…”

Section: Discussionmentioning

confidence: 99%

“…Drugs were initially dissolved in absolute ethanol (final concentration was 2%) and Tween 80 (2%) and brought to the final volume with saline (0.9% NaCl). The solution made of ethanol, Tween 80, and saline was also used as the vehicle [ 27 , 28 ]. Drugs were administered by intraperitoneal injection at a volume of 4 µL/g.…”

Section: Methodsmentioning

confidence: 99%

“…Drugs were administered by intraperitoneal injection at a volume of 4 µL/g. In this trial, as already described in previous safety pharmacological studies on NPS [ 27 , 28 , 29 ], a wide range of doses was used for DOB (0.01–30 mg/kg) and PMA (0.01–30 mg/kg) for the purpose of better evaluating the behavioral effects of the two compounds on sensorimotor responses, prepulse inhibition studies, and spontaneous locomotion.…”

Section: Methodsmentioning

confidence: 99%

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Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

et al. 2020

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The drastic increase in hallucinogenic compounds in illicit drug markets of new psychoactive substances (NPS) is a worldwide threat. Among these, 2, 5-dimetoxy-4-bromo-amphetamine (DOB) and paramethoxyamphetamine (PMA; marketed as “ecstasy”) are frequently purchased on the dark web and consumed for recreational purposes during rave/dance parties. In fact, these two substances seem to induce the same effects as MDMA, which could be due to their structural similarities. According to users, DOB and PMA share the same euphoric effects: increasing of the mental state, increasing sociability and empathy. Users also experienced loss of memory, temporal distortion, and paranoia following the repetition of the same thought. The aim of this study was to investigate the effect of the acute systemic administration of DOB and PMA (0.01–30 mg/kg; i.p.) on motor, sensorimotor (visual, acoustic, and tactile), and startle/PPI responses in CD-1 male mice. Moreover, the pro-psychedelic effect of DOB (0.075–2 mg/kg) and PMA (0.0005–0.5 mg/kg) was investigated by using zebrafish as a model. DOB and PMA administration affected spontaneous locomotion and impaired behaviors and startle/PPI responses in mice. In addition, the two compounds promoted hallucinatory states in zebrafish by reducing the hallucinatory score and swimming activity in hallucinogen-like states.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

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“…These new drugs are not subjected to clinical trials and information concerning toxicity and specific associated effects is still limited. Yet, animal and human studies showed that NPS are able to elicit not only rewarding and reinforcing effects [ 15 , 16 , 17 , 18 ], but also toxic effects of varying severity, at both the peripheral and central levels [ 19 , 20 ], despite an apparent, hazardous perception of safety [ 21 ]. Most of them are synthetic cannabinoids and cathinones, new hallucinogen and dissociative drugs or synthetic opioids, these latter representing a major source of social and clinical alarm, due to the numerous fatalities and intoxications associated with their use [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

et al. 2020

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Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of “classic” drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood.

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“…Acute administration demonstrates that MPA acts as a dopaminergic and noradrenergic stimulating drug. MPA stimulates locomotor activity by increasing the heart rate, breath rate, and blood pressure 31 …”

Section: Introductionmentioning

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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Methiopropamine and its acute behavioral effects in mice: is there a gray zone in new psychoactive substances users?

Cited by 20 publications

References 103 publications

Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

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

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