Addressing Hazards from Unscheduled Novel Psychoactive Substances as Research Chemicals: The Case of U-50488

Amin, Zubair; Rambaran, Kerry Anne; Fleming, Steven W.; Cho, Kevin; Chacko, Liza; Alzghari, Saeed K

doi:10.7759/cureus.1914

Cited by 3 publications

(9 citation statements)

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“…U-50488 or (2-(3,4-dichlorophenyl)- N -methyl- N -[(1R,2R)-2-pyrrolidin-1-ylcyclohexyl] acetamide) (Figure 3D) is an NSO developed by Upjohn in the 1970s as a κ-selective derivative of U-47700 [67]. Studies in animals have shown that U-50488 causes diuresis and dysphoria rather than respiratory depression or constipation [67]. It shows agonist activity on the κ-opioid receptor, with some reported μ-opioid receptor respiratory antagonist effects [30].…”

Section: Resultsmentioning

confidence: 99%

Novel synthetic opioids – toxicological aspects and analysis

Tabarra

Soares

Rosado

et al. 2019

Forensic Sciences Research

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Over the past few years, there has been an emerging number of new psychoactive drugs. These drugs are frequently mentioned as “legal highs”, “herbal highs”, “bath salts” and “research chemicals”. They are mostly sold and advertised on online forums and on the dark web. The emerging new psychoactive substances are designed to mimic the effects of psychoactive groups, which are often abused drugs. Novel synthetic opioids are a new trend in this context and represent an alarming threat to public health. Given the wide number of fatalities related to these compounds reported within the last few years, it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related substances. Clinicians dealing with fentanyl intoxication cases should consider that it could, in fact, be a fentanyl analogue. For this reason, it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures, including analysis in alternative matrices, if available, to investigate poly-drug use and possible tolerance to opioids. To address this public health problem, better international collaboration, effective legislation, effective investigation, control of suspicious “research chemicals” online forums and continuous community alertness are required. This article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology, metabolism, posology, available forms, as well as their toxic effects, highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.

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Section: Resultsmentioning

confidence: 99%

Novel synthetic opioids – toxicological aspects and analysis

Tabarra

Soares

Rosado

et al. 2019

Forensic Sciences Research

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“…Compounds such as U-47700, U-51754, U-49900, U-448800, AH-7921 from the chemical family of benzamide, U-50488 and U-51754 from the acetamide family and MT-45 from the piperazine family are the NSOs most recently reported as health threats for opioids consumers ( Mohr et al, 2016 ; Amin et al, 2017 ; Baumann et al, 2017 ; Domanski et al, 2017 ; Fabregat-Safont et al, 2017 ; Prekupec et al, 2017 ; Marchei et al, 2018 ). Indeed, this new generation of derivatives has been involved in a number of recent overdose deaths worldwide ( Drug Enforcement Administration [DEA], 2016 ; Baumann et al, 2017 ; Domanski et al, 2017 ; Fabregat-Safont et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…Information about U-50488 and U-51754 is quite scant. These acetamides are U-47700 related compounds, being part of the trans -1,2-diamine opioid analgesic chemical class synthesized by the Upjohn Company in the attempt to produce a non-addicting analgesic as potent as morphine ( Mohr et al, 2016 ; Amin et al, 2017 ; Domanski et al, 2017 ; Fleming et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…In animal models, U-50488 has been studied for its diuretic, antitussive, analgesic and anticonvulsant properties, but it is known to induce dysphoria and stress-like effects in rodents ( Muschamp et al, 2012 ; Mohr et al, 2016 ; Amin et al, 2017 ). U-50488 abuse potential is unknown and at present this synthetic opioid is an uncontrolled substance available online from companies selling research chemicals ( Mohr et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…U-50488 abuse potential is unknown and at present this synthetic opioid is an uncontrolled substance available online from companies selling research chemicals ( Mohr et al, 2016 ). Currently, information about the toxicological profile and toxicoepidemiology of U-50488 is poor, although the structural similarity of U-50488 to U-47700 poses users at potential health risks associated with its abuse and easy accessibility ( Amin et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacotoxicology of Non-fentanyl Derived New Synthetic Opioids

et al. 2018

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A class of opioid agonists not structurally related to fentanyl, derived from research publications of pharmaceutical companies or patents within the United States and abroad are contributing to the current opioid epidemic. Novel synthetic opioids (NSOs) created to circumvent drug control laws such as U-47700, U-49900, AH-7921, or MT-45 have no recognized therapeutic use, are clandestinely manufactured and sold on conventional or dark web. We herein provide a review of the pharmacological properties available on most of these substances trying to provide a better knowledge on these compounds, particularly with respect to toxicity and dangerous adverse effects in users. Indeed, these NSOs share not only a great potency of action and receptor affinity with respect to natural or synthetic opiates (e.g., morphine, heroin, and methadone) but also a non-negligible toxicity leading to intoxications and fatalities, posing a serious harm to public health and society.

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Synthetic opioids: a review and clinical update

Shafi

Berry

Sumnall

et al. 2022

Therapeutic Advances in Psychopharmacology

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The term ‘opioids’ refers to both the natural compounds (‘opiates’) which are extracted from the opium poppy plant ( Papaver somniferum) and their semi-synthetic and synthetic derivatives. They all possess relatively similar biochemical profiles and interact with the opioid receptors within the human body to produce a wide range of physiological effects. They have historically been used for medicinal purposes, their analgesic and sedative effects, and in the management of chronic and severe pain. They have also been used for non-medicinal and recreational purposes to produce feelings of relaxation, euphoria and well-being. Over the last decade, the emergence of an illegal market in new synthetic opioids has become a major global public health issue, associated with a substantial increase in unintentional overdoses and drug-related deaths. Synthetic opioids include fentanyl, its analogues and emerging non-fentanyl opioids. Their popularity relates to changes in criminal markets, pricing, potency, availability compared to classic opioids, ease of transport and use, rapid effect and lack of detection by conventional testing technologies. This article expands on our previous review on new psychoactive substances. We now provide a more in-depth review on synthetic opioids and explore the current challenges faced by people who use drugs, healthcare professionals, and global public health systems.

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Addressing Hazards from Unscheduled Novel Psychoactive Substances as Research Chemicals: The Case of U-50488

Cited by 3 publications

References 4 publications

Novel synthetic opioids – toxicological aspects and analysis

Novel synthetic opioids – toxicological aspects and analysis

Pharmacotoxicology of Non-fentanyl Derived New Synthetic Opioids

Synthetic opioids: a review and clinical update

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