Cannabimimetic activities of cumyl carboxamide-type synthetic cannabinoids

Asada, Akiko; Doi, Takahiro; Tagami, Takaomi; Satsuki, Yuka; Kawaguchi, Masami; Nakamura, Akihiko; Sawabe, Yoshiyuki

doi:10.1007/s11419-017-0374-9

Cited by 17 publications

(38 citation statements)

References 6 publications

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“…5F-Cumyl-PINACA as an active substance at m/z 367 by comparing the molecular ion signal as well as the fragment pattern [35]. For direct measurement of the herbal mixture, a S/N ratio of 50.9 was calculated for the base peak at m/z 352 and a S/N ratio of 3.7 for the molecular ion signal at m/z 367.…”

Section: New Psychoactive Substance On Herbal Mixturementioning

confidence: 99%

“…Strong EI fragmentation signal at low m/z are typical when investigating complex natural samples. Direct measurement of the investigated herbal mixture revealed the usage of 5F-Cumyl-PINACA as an active substance at m/z 367 by comparing the molecular ion signal as well as the fragment pattern [35]. For direct measurement of the herbal mixture, a S/N ratio of 50.9 was calculated for the base peak at m/z 352 and a S/N ratio of 3.7 for the molecular ion signal at m/z 367.…”

Section: Additional Capabilities Of the Apld Approachmentioning

confidence: 99%

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Ambient Pressure Laser Desorption—Chemical Ionization Mass Spectrometry for Fast and Reliable Detection of Explosives, Drugs, and Their Precursors

et al. 2018

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Fast and reliable information is crucial for first responders to draw correct conclusions at crime scenes. An ambient pressure laser desorption (APLD) mass spectrometer is introduced for this scenario, which enables detecting substances on surfaces without sample pretreatment. It is especially useful for substances with low vapor pressure and thermolabile ones. The APLD allows for the separation of desorption and ionization into two steps and, therefore, both can be optimized separately. Within this work, an improved version of the developed system is shown that achieves limits of detection (LOD) down to 500 pg while remaining fast and flexible. Furthermore, realistic scenarios are applied to prove the usability of this system in real-world issues. For this purpose, post-blast residues of a bomb from the Second World War were analyzed, and the presence of PETN was proven without sample pretreatment. In addition, the analyzable substance range could be expanded by various drugs and drug precursors. Thus, the presented instrumentation can be utilized for an increased number of forensically important compound classes without changing the setup. Drug precursors revealed a LOD ranging from 6 to 100 ng. Drugs such as cocaine hydrochloride, heroin, (3,4-methylendioxy-methamphetamine) hydrochloride (MDMA) hydrochloride, and others exhibit a LOD between 10 to 200 ng.

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Section: New Psychoactive Substance On Herbal Mixturementioning

confidence: 99%

Section: Additional Capabilities Of the Apld Approachmentioning

confidence: 99%

Ambient Pressure Laser Desorption—Chemical Ionization Mass Spectrometry for Fast and Reliable Detection of Explosives, Drugs, and Their Precursors

et al. 2018

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“…5 One class of SCRAs increasingly identified by forensic scientists and clinical toxicologists are heteroaromatic carboxamides containing a pendant cumylamine group. [6][7][8][9] The Slovenian National Focal Point notified the identification of 5F-CUMYL-PICA (5) through the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) early warning system (EWS) on September 23, 2014. 10 The indazole analog of 5F-CUMYL-PICA, 5F-CUMYL-PINACA (6), was notified by the Swedish EWS participants several weeks later.…”

mentioning

confidence: 99%

“…10 These compounds were previously reported in a 2014 patent as SGT-67 and SGT-25, respectively. 11 Unexpectedly, 5F-CUMYL-P7AICA (7), containing a 7-azaindole (pyrrolo [2,3-b]pyridine) core rather than an indole or indazole, was notified to the EWS in February 2015. 12 5F-CUMYL-P7AICA does not appear in patent WO2014167530 or elsewhere in historical chemical literature, and may be the product of rational design by unknown parties.…”

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confidence: 99%

Synthesis and pharmacology of new psychoactive substance 5F‐CUMYL‐P7AICA, a scaffold‐ hopping analog of synthetic cannabinoid receptor agonists 5F‐CUMYL‐PICA and 5F‐CUMYL‐PINACA

Banister

Adams

Kevin

et al. 2018

Drug Testing and Analysis

104

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Synthetic cannabinoid receptor agonists (SCRAs) are a dynamic class of new psychoactive substances (NPS), with novel chemotypes emerging each year. Following the putative detection of 5F-CUMYL-P7AICA in Australia in 2016, the scaffold-hopping SCRAs 5F-CUMYL-PICA, 5F-CUMYL-PINACA, and 5F-CUMYL-P7AICA were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). Since little is known of the pharmacology of 7-azaindole SCRAs like 5F-CUMYL-P7AICA, the binding affinities and functional activities of all compounds at cannabinoid type 1 and type 2 receptors (CB and CB , respectively) were assessed using tritiated radioligand competition experiments and fluorescence-based plate reader membrane potential assays. Despite CB binding affinities differing by over two orders of magnitude (K = 2.95-174 nM), all compounds were potent and efficacious CB agonists (EC = 0.43-4.7 nM), with consistent rank order for binding and functional activity (5F-CUMYL-PINACA >5F-CUMYL-PICA >5F-CUMYL-P7AICA). Additionally, 5F-CUMYL-P7AICA was found to exert potent cannabimimetic effects in mice, inducing hypothermia (6°C, 3 mg/kg) through a CB -dependent mechanism.

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“…These compounds degraded into a wide range of products, including quinoline, indole, naphthalene, and 1-naphthol. However, the synthetic cannabinoid landscape is increasingly diverse, and now includes a range of indole-, indazole-, and 7-azaindole-carboxamides with pendant cumyl or methyl valinate and methyl tert -leucinate groups, among others [22–24]. …”

Section: Introductionmentioning

confidence: 99%

Toxic by design? Formation of thermal degradants and cyanide from carboxamide-type synthetic cannabinoids CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18 during exposure to high temperatures

et al. 2018

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Purpose The use of novel synthetic cannabinoids as intoxicants continues in spite of associated health risks. These compounds are typically smoked or vaporized, but many synthetic cannabinoids contain thermally labile chemical moieties. This study investigated the thermal stability six carboxamide-type synthetic cannabinoids (CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18) in order to characterise potential user exposure to thermolysis products. Methods Compounds were heated sequentially to 200, 400, 600 and 800 °C using a thermolysis probe, and the resultant thermolysis products were analysed via GC–MS. A secondary analysis quantified thermolytically generated cyanide via LC–MS/MS. Results All six synthetic cannabinoids underwent thermal degradation when heated above 400 °C, and released a variety of potentially toxic products, including toluene, naphthalene, and 1-naphthalamine. Compound-specific degradants were tentatively identified together with a general degradative pathway for carboxamide-type synthetic cannabinoids, which proceeds via indole- or indazole-amide formation and subsequent dehydration to an indole- or indazole-carbonitrile. This degradative pathway culminated in the thermolytic liberation of cyanide, in amounts up to 27 μg per mg of starting material. Conclusions People who smoke carboxamide-type synthetic cannabinoids are likely to be exposed to range of potentially toxic thermal degradants, including cyanide. These degradants could have significant health impacts in human users.

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Cannabimimetic activities of cumyl carboxamide-type synthetic cannabinoids

Cited by 17 publications

References 6 publications

Ambient Pressure Laser Desorption—Chemical Ionization Mass Spectrometry for Fast and Reliable Detection of Explosives, Drugs, and Their Precursors

Ambient Pressure Laser Desorption—Chemical Ionization Mass Spectrometry for Fast and Reliable Detection of Explosives, Drugs, and Their Precursors

Synthesis and pharmacology of new psychoactive substance 5F‐CUMYL‐P7AICA, a scaffold‐ hopping analog of synthetic cannabinoid receptor agonists 5F‐CUMYL‐PICA and 5F‐CUMYL‐PINACA

Toxic by design? Formation of thermal degradants and cyanide from carboxamide-type synthetic cannabinoids CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18 during exposure to high temperatures

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