Toxicity and behavioural effects of ocfentanil and 2-furanylfentanyl in zebrafish larvae and mice

Bilel, Sabrine; Murari, Matilde; Pesavento, Sara; Arfè, Raffaella; Tirri, Micaela; Torroni, Lorena; Marti, Matteo; Tagliaro, Franco; Gottardo, Rossella

doi:10.1016/j.neuro.2023.01.003

Cited by 2 publications

(1 citation statement)

References 38 publications

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“…For the morphological evaluation, the concentration of 1 μM was chosen on the bases of a previous study performed by our group on fentanyl and other fentanyl analogs. 17,21 The assay showed that the survival rate of zebrafish embryos treated with the different synthetic opioids was higher than 87%, indicating that the synthetic opioids have low toxicity towards common cells.…”

Section: Discussionmentioning

confidence: 99%

Study of metabolism and potential toxicity of nine synthetic opioid analogs using the zebrafish larvae model

Murari,

Pesavento,

Greco

et al. 2023

Drug Testing and Analysis

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The use of novel psychoactive substances (NPSs) has dramatically increased worldwide, and among them, synthetic opioids are one of the fastest growing groups, where cinnamylpiperazines and 2‐benzylbenzimidazoles represent two of the most relevant subclasses. However, the data on their toxicity and metabolism are still limited. The aim of the present study was to evaluate the toxicity and metabolic pathways of some compounds belonging to these families, namely, AP‐237, 2‐methyl AP‐237, isotonitazene, flunitazene, etodesnitazene, metonitazene, metodesnitazene, N‐pyrrolidino etonitazene, and butonitazene. The study was performed using a zebrafish early life stages model. In fact, zebrafish (Danio rerio) embryos and larvae have recently been recognized as a suitable animal model in alternative to mammals, because they require less time and resources and do not need complex procedures for ethics approval. The cellular toxicity after a single administration was assessed at the fourth day post‐fertilization with acridine orange staining. Possible morphological defects were evaluated with a light microscope after 24 h of exposure to 1 μmol/L concentration of each drug. Subsequently, the larvae were euthanized and underwent analysis of drug metabolites using UPLC coupled to an Orbitrap high‐resolution mass spectrometer. High rates of morphological defects, as well as of cellular death, were detected, but no significant difference in mortality between treatment and control groups was observed. In addition, several metabolites, mainly produced through monohydroxylation, N‐dealkylation, and O‐dealkylation, were identified in the larvae extracts.

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Section: Discussionmentioning

confidence: 99%

Study of metabolism and potential toxicity of nine synthetic opioid analogs using the zebrafish larvae model

Murari,

Pesavento,

Greco

et al. 2023

Drug Testing and Analysis

View full text Add to dashboard Cite

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A Review of Toxicological Profile of Fentanyl—A 2024 Update

Williamson,

Kermanizadeh

2024

Toxics

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Fentanyl and its analogues are synthetic opioids of varying potencies that are unfortunately heavily abused. Over the last 15 years, fentanyl and its analogues have contributed to the increasing prominence of hospitalisation and numerous deaths due to drug overdose. In this comprehensive literature review, the mechanism of toxicity of the drug in humans is evaluated. A systematic approach was used whereby the relevant literature has been detailed where the toxicity of fentanyl and/or its analogues to different organs/systems were investigated. Furthermore, the review covers the post-mortem toxicological data and demographic information from past fatal cases where fentanyl was believed to be involved. Such insight into fentanyl toxicity is useful as an aid to better understand the toxic doses of the drug and the suspected mechanism of action and the unexpected complications associated with overdose incidences involving the drug. Finally, the review offers an overview of the traditional and emerging test systems used to investigate the adverse effects of fentanyl on human health.

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Toxicity and behavioural effects of ocfentanil and 2-furanylfentanyl in zebrafish larvae and mice

Cited by 2 publications

References 38 publications

Study of metabolism and potential toxicity of nine synthetic opioid analogs using the zebrafish larvae model

Study of metabolism and potential toxicity of nine synthetic opioid analogs using the zebrafish larvae model

A Review of Toxicological Profile of Fentanyl—A 2024 Update

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