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Cited by 32Forensic Toxicology and Drug AnalysisAlkaloids: synthesis and pharmacologyOpioid Use Disorder Treatment

In vitro and in vivo pharmacological characterization of the synthetic opioid MT-45

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Bilel, S, Azevedo, NJ, Arfè, R, Tirri, M, Gregori, A, Serpelloni, G, De-Giorgio, F, Frisoni, P +3 more·2020·Neuropharmacology
DOI 10.1016/j.neuropharm.2020.108110
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Abstract

MT-45 is a synthetic opioid that was developed in the 1970s as an analgesic compound. However, in recent years MT-45 has been associated with multiple deaths in Europe and has been included in the class of novel psychoactive substances known as novel synthetic opioids (NSOs). Little is known about the pharmaco-toxicological effects of MT-45. Therefore, we used a dynamic mass redistribution (DMR) assay to investigate the pharmacodynamic profile of this NSO in vitro compared with morphine. We then used in vivo studies to investigate the effect of the acute systemic administration of MT-45 (0.01–15 mg/kg i.p.) on motor and sensorimotor (visual, acoustic and tactile) responses, mechanical and thermal analgesia, muscle strength and body temperature in CD-1 male mice. Higher doses of MT-45 (6–30 mg/kg i.p.) were used to investigate cardiorespiratory changes (heart rate, respiratory rate, SpO2 saturation and pulse distention). All effects of MT-45 were compared with those of morphine. In vitro DMR assay results demonstrated that at human recombinant opioid receptors MT-45 behaves as a potent selective mu agonist with a slightly higher efficacy than morphine. In vivo results showed that MT-45 progressively induces tail elevation at the lowest dose tested (0.01 mg/kg), increased mechanical and thermal antinociception (starting from 1 to 6 mg/kg), decreased visual sensorimotor responses (starting from 3 to 6 mg/kg) and reduced tactile responses, modulated motor performance and induced muscle rigidity at higher doses (15 mg/kg). In addition, at higher doses (15–30 mg/kg) MT-45 impaired the cardiorespiratory functions. All effects were prevented by the administration of the opioid receptor antagonist naloxone. These findings reveal the risks associated with the ingestion of opioids and the importance of studying these drugs and undertaking more clinical studies of the current molecules to better understand possible therapeutic interventions in the case of toxicity.

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  • In the context of NPS, this is reminiscent of the identification of halogenated analogues of the synthetic cannabinoid receptor agonist JWH-018.

    “In the context of NPS, this is reminiscent of the identification of halogenated analogues of the synthetic cannabinoid receptor agonist JWH-018 (Barbieri et al., 2016; Sabrine Bilel et al., 2020; Vigolo et al., 2015).”

    From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Sabrine Bilel et al., 2020

    The Introduction identifies synthetic cannabinoids as a class of novel psychoactive substances, but does not discuss the identification of halogenated JWH-018 analogues. A References entry names Vigolo et al. (2015), a study of halogenated JWH-018 derivatives; the MT-45 paper’s own text does not report the claimed identification (pages not provided). (LLM, conf=0.73)

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Authors
Bilel, S., Azevedo, N., Arfè, R., Tirri, M., Gregori, A., Serpelloni, G., De-Giorgio, F., Frisoni, P., Neri, M., Calò, G., & Marti, M.
Affiliations
  • University of Ferrara (IT)
  • Università Cattolica del Sacro Cuore (IT)
  • Arma dei Carabinieri (IT)
  • University of Florida Health (US)
Corresponding author
Marti, M
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2020-07
Volume
171
Pages
108110
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2020.108110
OpenAlex
W3020153034
Semantic Scholar
66a07997352673681a45882d98878d37dcd01a89
Cited by
32
References
108
Citations by year
2026: 1 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 5
FWCI
3.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropharmacology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by-nc-nd)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
Funders
  • University of Ferrara (FIRB 2012)
  • Italian Ministry of Education, University and Research (RBFR12LDOW)
  • Catholic University of Rome
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords
synthetic opioids, new psychoactive substances, mu-opioid receptor agonists, morphine comparison, antinociception, sensorimotor deficits, motor impairment, muscle rigidity, cardiorespiratory depression, naloxone reversal, opioid toxicity
MeSH terms
Aggression, Analgesics, Opioid, Animals, Cricetulus, Dose-Response Relationship, Drug, Cricetinae, Hot Temperature, Hemodynamics, Humans, Morphine, Motor Activity, Naloxone, Narcotic Antagonists, Pain Measurement, Physical Stimulation, Piperazines, Receptors, Opioid, Respiration, Sensation, CHO Cells, Mice, Muscle Strength

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