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Nitrosyl factors play a vital role in the ventilatory depressant effects of fentanyl in freely moving guinea pigs.
Biomed Pharmacother
January 2025
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
An understanding of intracellular mechanisms by which fentanyl and other synthetic opioids exert adverse effects on breathing is needed. Using freely moving adult male guinea pigs, we administered the nitric oxide synthase (NOS) inhibitor, L-NAME (N-nitro-L-arginine methyl ester), to determine whether nitrosyl factors, such as nitric oxide and S-nitrosothiols, play a role in fentanyl-induced respiratory depression. Ventilatory parameters were recorded by whole body plethysmography to determine the effects of fentanyl (75 μg/kg, IV) in guinea pigs that had received a prior injection of vehicle (saline), L-NAME or the inactive D-isomer, D-NAME (both at 50 μmol/kg, IV), 15 min beforehand.
View Article and Find Full Text PDFThe Rise of Fentanyl: Molecular Aspects and Forensic Investigations.
Int J Mol Sci
January 2025
Legal Medicine, Department of Medical, Surgical and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.
Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl's medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications.
View Article and Find Full Text PDFDevelopment and preclinical testing of a naloxone prodrug depot for extended protection against opioid overdose.
Nat Commun
January 2025
Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA, US.
The opioid crisis, driven by synthetic opioids like fentanyl, demands innovative solutions. The opioid antidote naloxone has a short action ( ~ 1 hour), requiring repeated doses. To address this, we present a new and simple naloxone prodrug delivery system repurposing a hydrophilic derivative of acoramidis, a potent transthyretin ligand.
View Article and Find Full Text PDFCharacteristics of supervised injection site clients and factors associated with requiring overdose intervention, Montreal, Canada, 2018-2022.
Int J Drug Policy
January 2025
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900 rue St-Denis, Montréal, Québec H2X 0A9, Canada; Department of Emergency and Family Medicine, Université de Montréal, 2900 blvd Edouard Montpetit, Montréal, Québec H3T 1J4, Canada; National Drug and Alcohol Research Centre, UNSW Sydney, Anzac Parade, Kensington NSW 2052, Australia. Electronic address:
Background: Supervised injection sites (SIS) offer a hygienic environment in which people can inject drugs under observation; as such, these harm reduction services have been on the forefront of the overdose epidemic. We sought to understand factors predictive of an overdose requiring an emergency response intervention at SIS in Montréal, Canada.
Methods: We used administrative data from all four Montréal SIS from 1 March 2018 - 31 October 2022 to first calculate the rate of onsite overdose requiring intervention (e.
Development and Application of a Comprehensive Non-targeted Screening Strategy for Fentanyl Analogues.
J Hazard Mater
January 2025
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China; Key Laboratory of Monitoring and Assessment on Novel Food Raw Materials, State Administration for Market Regulation, Chengdu 611130, China. Electronic address:
The growing abuse of fentanyl and its analogues (FTNs) presents a substantial public health threat, prompting the introduction of regulatory controls by government authorities. Nevertheless, existing screening strategies for FTNs are primarily based on targeted or non-targeted approaches that utilize a limited set of mass spectrometry fragmentation data, which are far from meeting the needs of class scheduling. In this study, a comprehensive non-targeted screening strategy for FTNs was developed.
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