Carfentanil – from an animal anesthetic to a deadly illicit drug

Zawilska, Jolanta B.; Kuczyńska, Katarzyna; Kosmal, Wiktoria; Markiewicz, K; Adamowicz, Piotr

doi:10.1016/j.forsciint.2021.110715

Cited by 32 publications

(32 citation statements)

References 54 publications

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“…Moreover, almost 30% of cases were intentional drug abuses to commit suicide [ 19 ]. This brief statistical overview is in good agreement with data described in the literature, which confirm that opioid intoxications are a global problem [ 8 , 12 , 16 , 17 , 20 , 21 , 22 , 23 , 24 ].…”

Section: Introductionsupporting

confidence: 88%

“…According to our literary research, there has not been a published study about metabolic pathways of this drug in vivo in humans. Identification of twelve metabolites of carfentanyl was done using human liver microsomes and human hepatocytes [ 22 , 29 , 45 ]. N -demethylation as the main biotransformation was predicted in silico and confirmed by high-resolution mass spectrometry.…”

Section: Introductionmentioning

confidence: 99%

“…N -demethylation as the main biotransformation was predicted in silico and confirmed by high-resolution mass spectrometry. Carfentanyl and its metabolite, norfentanyl, may accumulate in the human body, which can cause resistance to the antidote [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Electroanalysis of Fentanyl and Its New Analogs: A Review

et al. 2022

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The review describes fentanyl and its analogs as new synthetic opioids and the possibilities of their identification and determination using electrochemical methods (e.g., voltammetry, potentiometry, electrochemiluminescence) and electrochemical methods combined with various separation methods. The review also covers the analysis of new synthetic opioids, their parent compounds, and corresponding metabolites in body fluids, such as urine, blood, serum, and plasma, necessary for a fast and accurate diagnosis of intoxication. Identifying and quantifying these addictive and illicit substances and their metabolites is necessary for clinical, toxicological, and forensic purposes. As a reaction to the growing number of new synthetic opioid intoxications and increasing fatalities observed over the past ten years, we provide thorough background for developing new biosensors, screen-printed electrodes, or other point-of-care devices.

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Section: Introductionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Electroanalysis of Fentanyl and Its New Analogs: A Review

et al. 2022

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“…Furthermore, increasingly potent fentanyl analogs have been reported in the illicit market, including carfentanil, an opioid 10,000 times more potent than morphine, which is used as a large animal anesthetic in veterinary medicine. 4,5 The ongoing global pandemic of novel coronavirus disease 2019 (COVID- 19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has intersected with the opioid crisis and worsened it.…”

Section: Introductionmentioning

confidence: 99%

Development of Novel Video-Based First Responder Opioid Hazard Refresher Training

et al. 2021

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First responders encounter many hazards in the execution of their duties, and exposure to hazardous materials such as opioids is a primary safety concern. The ongoing opioid crisis in the United States continues to be a major public health issue, with overdose deaths from opioids reaching epidemic levels. Although responders frequently encounter opioids, available data on safety and risk are not always well-communicated, and we identified a need for refresher and just-in-time training products on this topic. In response, we created a training video series that is informative, concise, and visually appealing. The video series, available on YouTube, was tested with a small initial population, with findings suggesting key questions for a larger study focused on integration of the refresher training with existing programs to optimize retention and adoption of safety practices.

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“…The 3-and 4-positions on the piperidine ring of the fentanyl scaffold have been exploited to develop more potent fentanyl analogs, including carfentanil, 3-methylfentanyl, and lofentanil (Stanley, 2014;Van Bever et al, 1974). In particular, carfentanil has evolved from being used as an animal anesthetic to a deadly abused drug (Zawilska et al, 2021), and even has the potential of being used as a chemical weapon (Wax et al, 2003). Intriguingly, with the same addition of a 3-methyl moiety, 3-methylfentanyl has much higher potency (as high as ~200-fold, (3R,4S)-isomer) than fentanyl (Jin et al, 1981;Xu et al, 1991), while lofentanil (i.e., 3methylcarfetanil) only has slightly better affinity at the MOR than carfentanil (Maguire et al, 1992;Yeadon and Kitchen, 1988).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive evaluation of the potential binding poses of fentanyl and its analogs at the µ-opioid receptor

Xie

Goldberg

Shi

2021

Preprint

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Fentanyl and its analogs are selective agonists of the µ-opioid receptor (MOR). Among novel synthetic opioids (NSOs), they dominate the recreational drug market and are the main culprits for the opioid crisis, which has been exacerbated by the COVID-19 pandemic. By taking advantage of the crystal structures of the MOR, several groups have investigated the binding mechanism of fentanyl, but have not reached a consensus, in terms of both the binding orientation and the fentanyl conformation. Thus, the binding mechanism of fentanyl at the MOR remains an unsolved and challenging question. Here, we carried out a systematic computational study to investigate the preferred fentanyl conformations, and how these conformations are being accommodated in the MOR binding pocket. We characterized the free energy landscape of fentanyl conformations with metadynamics simulations, as well as performed long-timescale molecular dynamics simulations to compare and evaluate several possible fentanyl binding conditions. Our results indicate that the most preferred binding pose in the MOR binding pocket corresponds well with the minima on the energy landscape of fentanyl in the absence of the receptor, while the energy landscape can be reconfigured by modifying the fentanyl scaffold. The interactions with the receptor may stabilize a slightly unfavored fentanyl conformation in an alternative binding pose. By extending similar investigations to fentanyl analogs, our findings establish a structure-activity relationship of fentanyl binding at the MOR. In addition to providing a structural basis to understand the potential toxicity of the emerging NSOs, such insights will contribute to developing new, safer analgesics.

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Carfentanil – from an animal anesthetic to a deadly illicit drug

Cited by 32 publications

References 54 publications

Electroanalysis of Fentanyl and Its New Analogs: A Review

Electroanalysis of Fentanyl and Its New Analogs: A Review

Development of Novel Video-Based First Responder Opioid Hazard Refresher Training

A comprehensive evaluation of the potential binding poses of fentanyl and its analogs at the µ-opioid receptor

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