U-47700: An Emerging Threat

Alzghari, Saeed K; Fleming, Steven W.; Rambaran, Kerry Anne; Long, James E.; Burkhart, Samantha; An, Jie; Furmaga, Jakub

doi:10.7759/cureus.1791

Cited by 7 publications

(7 citation statements)

References 4 publications

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“…The much higher binding affinities of NSOs result in strong psychoactive and unpredictable toxic effects, even if small doses are consumed. Numerous cases of intoxications have been reported with life-threatening conditions expressed by the classical triad of opioid intoxications, that is to say, respiratory depression, sedation, and miosis (Coopman et al 2016 ; Alzghari et al 2017 ; Fleming et al 2017 ; Rambaran et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

et al. 2021

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New synthetic opioids (NSOs) pose a public health concern since their emergence on the illicit drug market and are gaining increasing importance in forensic toxicology. Like many other new psychoactive substances, NSOs are consumed without any preclinical safety data or any knowledge on toxicokinetic (TK) data. Due to ethical reasons, controlled human TK studies cannot be performed for the assessment of these relevant data. As an alternative animal experimental approach, six pigs per drug received a single intravenous dose of 100 µg/kg body weight (BW) of U-47700 or 1000 µg/kg BW of tramadol to evaluate whether this species is suitable to assess the TK of NSOs. The drugs were determined in serum and whole blood using a fully validated method based on solid-phase extraction and LC–MS/MS. The concentration–time profiles and a population (pop) TK analysis revealed that a three-compartment model best described the TK data of both opioids. Central volumes of distribution were 0.94 L/kg for U-47700 and 1.25 L/kg for tramadol and central (metabolic) clearances were estimated at 1.57 L/h/kg and 1.85 L/h/kg for U-47700 and tramadol, respectively. The final popTK model parameters for pigs were upscaled via allometric scaling techniques. In comparison to published human data, concentration–time profiles for tramadol could successfully be predicted with single species allometric scaling. Furthermore, possible profiles for U-47700 in humans were simulated. The findings of this study indicate that unlike a multiple species scaling approach, pigs in conjunction with TK modeling are a suitable tool for the assessment of TK data of NSOs and the prediction of human TK data.

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Section: Introductionmentioning

confidence: 99%

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

et al. 2021

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“…U-47700 (IUPAC name: 3,4-dichloro- N -[2-(dimethylamino)cyclohexyl]- N -methylbenzamide) or 3,4-dichloro- N -[2-(dimethylamino)cyclohexyl]- N -methylbenzamide HCl, “pink”, or “U4’’ is 7.5 times more potent than morphine; it appears in powders, tablets, and liquids [7,22,70,83,103,104,105,106,107]. Typical routes of administration are oral, nasal, intrarectal, by smoking, intravenous injection or by combinations of these routes [106,108].…”

Section: Resultsmentioning

confidence: 99%

Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health

Lovrečič

Lovrečić

Gabrovec

et al. 2019

IJERPH

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Background: In the last decade there has been a progressive increase in the use of new psychoactive substances (NPSs) that are not yet under international control. In particular, novel synthetic opioids (NSOs) have reappeared on the recreational drug market in the last few years. As a result, the use of NSOs has increased rapidly. This poses an emerging and demanding challenge to public health. Aim: To raise awareness among clinicians and other professionals about NPSs, especially NSOs, to summarize current knowledge about pharmacological properties, forms of NSO on the market, pattern of use, effects and consequences of use. Methods: An electronic search was carried out on the Medline/PubMed and Google Scholar databases to find selected search terms. Results: Some NPSs are already controlled, while others can be legally sold directly on the drug market (mainly via internet, less so by drug dealers) or be used as precursors for the synthesis of other designer drugs that mimic the psychoactive effects of controlled substances. Potential side-effects of NSOs include miosis, sedation, respiratory depression, hypothermia, inhibition of gastrointestinal propulsion, death (from opioid overdose). Conclusions: The severity of the opioid crisis has intensified with the introduction of highly potent NSOs on the drug market. As long as addicts are dying from overdose or similar causes, there is something more constructive to do than waiting for addicts to overdose on heroin at a place located near a remedy, as if to say, within reach of naloxone.

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“…Drug users may be more likely to experiment with synthetic opioids (as they lack the stigma of heroin) or be exposed to them unwittingly owing to their inclusion as a co‐ingredient/substitute in synthetic formulations . As the use of synthetic compounds proliferates, along with “opioid epidemics,” any incidents involving potent “new” opioids are worrying . Easy availability at a low price together with addictive potential and a small margin of safety maybe a combination with potentially disastrous consequences at an individual, community, societal, and global levels.…”

Section: Resultsmentioning

confidence: 99%

“…Owing to the evident risks of fatal overdose and possible addictive potential, U‐47700 is an emergent threat to opioid (mis)users and therefore recent recommendations urge that awareness of this new synthetic opioid is raised among toxicologists (and across related disciplines) by reporting new cases as they arise and disseminating knowledge and education in this area . The present article reports the first formally recorded case of near‐fatal intoxication involving U‐47700 in Czech Republic.…”

mentioning

confidence: 93%

Near‐fatal Intoxication with the “New” Synthetic Opioid U‐47700: The First Reported Case in the Czech Republic

Židková

Horsley

Hloch

et al. 2018

Journal of Forensic Sciences

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Recreational use of the potent synthetic opioid 3,4- dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700) is rising, accompanied by increasingly frequent cases of serious intoxication. This article reports a case of near-fatal U-47700 intoxication. A man was found unconscious (with drug powder residues). After 40 h in hospital (including 12 h of supported ventilation), he recovered and was discharged. Liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or gas chromatography/mass spectrometry (GC/MS) were used to detect and quantify substances in powders, serum and urine. Powders contained U-47700 and two synthetic cannabinoids. Serum and urine were positive for U-47700 (351.0 ng/mL), citalopram (

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U-47700: An Emerging Threat

Cited by 7 publications

References 4 publications

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health

Near‐fatal Intoxication with the “New” Synthetic Opioid U‐47700: The First Reported Case in the Czech Republic

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