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

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Abstract

Methiopropamine is a structural analog of methamphetamine that is categorized as a novel psychoactive substance. It primarily acts as a norepinephrine–dopamine reuptake inhibitor and, secondarily, as a serotonin reuptake inhibitor. In humans, methiopropamine induces stimulation and alertness and increases focus and energy. However, significant side effects are reported, such as tachycardia, anxiety, panic attacks, perspiration, headache, and difficulty in breathing. To date, little data is available regarding its pharmacodynamic effects, thereby we aimed to investigate the acute in vivo effects induced by this drug on sensorimotor responses, body temperature, pain thresholds, motor activity, and cardiovascular and respiratory systems in CD-1 male mice. We selected a range of doses that correspond to the whole range of human reported use, in order to evaluate the threshold of adverse effects presentation. This study demonstrates that methiopropamine acts as a dopaminergic and noradrenergic stimulating drug and that the highest doses (10–30 mg/kg) impair the visual placing response, facilitate the acoustic and tactile response, induce hypothermia, increase mechanical and thermal analgesia, stimulate locomotor activity, induce motor stereotypies, and strongly affected cardiovascular and respiratory parameters, increasing heart rate, breath rate, and blood pressure but reducing oxygen saturation. On the contrary, lower doses do not show any of those effects. We hypothesize that there is a range of doses that do enhance performance but do not seem hazardous to users: this gap could induce the perception of safety and increase the abuser population.

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Abbreviations

NPS:

Novel psychoactive substances

MPA:

Methiopropamine

METH:

Methamphetamine

NE:

Norepinephrine

DA:

Dopamine

5-HT:

Serotonin

LC:

Locus coeruleus

CAP:

Compound action potential

WDT:

Workplace drug testing

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Funding

This study was funded by the Department of Anti-Drug Policies, of the Presidency of the Council of Ministers, Italy (project: “Effects of NPS: development of a multicentre research for the information enhancement of the Early Warning System” to M. Marti); local funds from the University of Ferrara (FAR 2016 and FAR 2017 to M. Marti); local funds from the Catholic University of Rome (Linea D1 2016 to F. De-Giorgio); and FIRB 2012 from the Italian Ministry of Education, University and Research (Grant no. RBFR12LDOW to F. De-Giorgio).

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Author notes

  1. Fabio De-Giorgio and Sabrine Bilel contributed equally to this work.

Authors and Affiliations

  1. Department of Health Care Surveillance and Bioethics, Section of Legal Medicine, Università Cattolica del Sacro Cuore, Rome, Italy

    Fabio De-Giorgio, Raffaella Arfè, Cristian Camuto & Federica Foti

  2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Fabio De-Giorgio

  3. Department of Morphology, Surgery and Experimental Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, via Fossato di Mortara 70, 44121, Ferrara, Italy

    Sabrine Bilel, Micaela Tirri, Raffaella Arfè, Paolo Frisoni, Margherita Neri & Matteo Marti

  4. Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy

    Claudio Trapella

  5. Laboratorio Antidoping, Federazione Medica Sportiva Italiana, Rome, Italy

    Cristian Camuto & Francesco Botrè

  6. Department of Experimental Medicine, “Sapienza” University, Rome, Italy

    Francesco Botrè

  7. Collaborative Center for the Italian National Early Warning System, Department of Anti-Drug Policies, Presidency of the Council of Ministers, Rome, Italy

    Matteo Marti

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  1. Fabio De-Giorgio
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  11. Matteo Marti
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Contributions

All authors contributed to the study conception and design. Material preparation, experiment sections, and data collection and analysis were performed by Sabrine Bilel, Micaela Tirri, Raffaella Arfè, Claudio Trapella, Cristian Camuto, Federica Foti, Paolo Frisoni, Margherita Neri, and Francesco Botrè. The first draft of the manuscript was written by Matteo Marti and Fabio De-Giorgio and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Matteo Marti.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in the studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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De-Giorgio, F., Bilel, S., Tirri, M. et al. Methiopropamine and its acute behavioral effects in mice: is there a gray zone in new psychoactive substances users?. Int J Legal Med 134, 1695–1711 (2020). https://doi.org/10.1007/s00414-020-02302-3

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