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Comparison of N-methyl-2-pyrrolidone (NMP) and the “date rape” drug GHB: behavioral toxicology in the mouse model

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Abstract

N-methyl-2-pyrrolidone (NMP) and γ-hydroxybutyrate acid (GHB) are synthetic solvents detected in the recreational drug market. GHB has sedative/hypnotic properties and is used for criminal purposes to compromise reaction ability and commit drug-facilitated sexual assaults and other crimes. NMP is a strong solubilizing solvent that has been used alone or mixed with GHB in case of abuse and robberies. The aim of this experimental study is to compare the acute pharmaco-toxicological effects of NMP and GHB on neurological signs (myoclonia, convulsions), sensorimotor (visual, acoustic, and overall tactile) responses, righting reflex, thermoregulation, and motor activity (bar, drag, and accelerod test) in CD-1 male mice. Moreover, since cardiorespiratory depression is one of the main adverse effects related to GHB intake, we investigated the effect of NMP and GHB on cardiorespiratory changes (heart rate, breath rate, oxygen saturation, and pulse distension) in mice. The present study demonstrates that NMP inhibited sensorimotor and motor responses and induced cardiorespiratory depression, with a lower potency and efficacy compared to GHB. These results suggest that NMP can hardly be used alone as a substance to perpetrate sexual assault or robberies.

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Abbreviations

DFCs:

Drug-facilitated crimes

DFSA:

Drug-facilitated sexual assault

GABA:

γ-Aminobutyric acid

GBL:

γ-Butyrolactone

GHB:

γ-Hydroxybutyric acid; 4-hydroxybutanoic acid; 4-hydroxybutyric acid

GHBR:

γ-Hydroxybutyrate receptor

GVL:

γ-Valerolactone

NMP:

N-methyl-2-pyrrolidone; 1-methyl-2-pyrrolidinone; N-methylpyrrolidone

2-P:

2-Pyrrolidone

HR:

Heart rate

BR:

Breath rate

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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 2017 and FAR 2019 to M. Marti), local funds from the Università Cattolica del Sacro Cuore (Linea D1 2019 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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Authors and Affiliations

Authors

Contributions

MM, AR, BS, contributed to the conception and design of the study. AR, BS, TM, performed in vivo experiments. MM, AR, BS, DEF, FDG, FF wrote the manuscript. AR, BS, MM, DEF, NM, FP, TM, AR, SG, NM, FDG, FF edited sections of the manuscript. AR, TM, BS, MM, GA, SG, performed statistical analysis. All authors contributed to manuscript revision, read, and approved the submitted version.

Corresponding authors

Correspondence to Fabio De-Giorgio or Matteo Marti.

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Ethical statements

All applicable international, national, and/or 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. Project activated in collaboration with the Presidency of the Council of Ministers-DPA Anti-Drug Policies (Italy).

Conflict of interest

The authors declare no competing interests.

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Arfè, R., Bilel, S., Tirri, M. et al. Comparison of N-methyl-2-pyrrolidone (NMP) and the “date rape” drug GHB: behavioral toxicology in the mouse model. Psychopharmacology 238, 2275–2295 (2021). https://doi.org/10.1007/s00213-021-05852-5

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  • DOI: https://doi.org/10.1007/s00213-021-05852-5

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