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- 4-CN CUMYL-BINACA
- DMF: 30 mg/ml
- DMF:PBS(pH7.2) (1:2): 0.25 mg/ml
- DMSO: 15 mg/ml
- Ethanol: 1 mg/ml
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SGT-78 / Buy SGT-78 online
SGT-78 / Buy SGT-78 online .CUMYL-4CN-BINACA (also known as CUMYL-CYBINACA or SGT-78) is an indazole-3-carboxamide based synthetic cannabinoid that has been sold online as a designer drug. It is a potent agonist for cannabinoid receptors CB1 and CB2, with in vitro EC50 values of 0.58 nM and 6.12 nM, respectively.In mice, CUMYL-4CN-BINACA produces hypothermic and pro-convulsant effects via the CB1 receptor, and anecdotal reports suggest it has an active dose of around 0.1 mg in humans.SGT-78 / Buy SGT-78 online
Synthetic cannabinoid receptor agonists (SCRAs) are the largest class of new psychoactive substances (NPS). New examples are detected constantly, and some are associated with a series of adverse effects, including seizures. CUMYL-4CN-BINACA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)indazole-3-carboxamide) is structurally related to potent, cumylamine-derived SCRAs such as 5F-CUMYL-PINACA, but is unusual due to a terminal aliphatic nitrile group not frequently encountered in SCRAs or pharmaceuticals. We report here that CUMYL-4CN-BINACA is a potent CB1 receptor agonist (K i = 2.6 nM; EC50 = 0.58 nM) that produces pro-convulsant effects in mice at a lower dose than reported for any SCRA to date (0.3 mg/kg, i.p). Hypothermic and pro-convulsant effects in mice could be reduced or blocked, respectively, by pretreatment with CB1 receptor antagonist SR141716, pointing to at least partial involvement of CB1 receptors in vivo. Pretreatment with CB2 receptor antagonist AM-630 had no effect on pro-convulsant activity. The pro-convulsant properties and potency of CUMYL-4CN-BINACA may underpin the toxicity associated with this compound in humans.
Keywords: novel psychoactive substance, new psychoactive substance, CUMYL, synthetic cannabinoid, seizure, convulsant.
SGT-78 / Buy SGT-78 online .CUMYL-4CN-BINACA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)indazole-3-carboxamide) (1), also known as 4CN-CUMYL-BUTINACA, CUMYL-CYBINACA, and SGT-78, has been available as a synthetic cannabinoid receptor agonist (SCRA) and new psychoactive substance (NPS) in the European Union and elsewhere since late 2015, with more than 2,400 seizures reported by nine countries (European Monitoring Centre for Drugs and Drug Addiction, 2017; Arıkan Ölmez et al., 2018). CUMYL-4CN-BINACA has been detected in multiple forms, including liquids and powders, with a single seizure of 50 kg of powder intercepted by Spanish customs en route from China (European Monitoring Centre for Drugs and Drug Addiction, 2017). Eleven fatalities with analytical confirmation of CUMYL-4CN-BINACA have occurred in the EU, withSGT-78 / Buy SGT-78 online attributed as cause or contributor to death in at least five of these (EMCDDA, 2017). In Turkey, CUMYL-4CN-BINACA was detected in 85 post-mortem blood samples collected from autopsies conducted in the latter half of 2016 (Yeter, 2017).
SGT-78 / Buy SGT-78 online .CUMYL-4CN-BINACA originates as example SGT-78 in a New Zealand patent from 2014 describing the preparation of cannabinoids for “treating pain and nausea, stimulating appetite, and inducing a positive mood change,” and its synthetic route is analogous to those reported for related compounds (Bowden and Williamson, 2014; Longworth et al., 2017). The SCRAs CUMYL-PINACA and 5F-CUMYL-PINACA (2), containing a pentyl or 5-fluoropentyl chain, respectively, in place of the 4-cyanobutyl group of CUMYL-4CN-BINACA, were reported in several cases of acute intoxication (Figure 1; Abouchedid et al., 2017; Dobaja et al., 2017). Unlike CUMYL-4CN-BINACA, no fatalities have been attributed to CUMYL-PINACA or 5F-CUMYL-PINACA. The structural characterization of CUMYL-4CN-BINACA was recently reported (Bovens et al., 2017), and CUMYL-4CN-BINACA metabolites have been identified in authentic urine samples and human liver microsomes .SGT-78 / Buy SGT-78 online
SGT-78 / Buy SGT-78 online .A nitrile group occurs in more than 30 approved pharmaceuticals; commonly as an aromatic nitrile, but less commonly as an aliphatic nitrile since the latter may release cyanide in vivo (Tanii and Hashimoto, 1984). Indeed, CUMYL-4CN-BINACA undergoes apparent metabolic nitrile hydrolysis, which may contribute to toxicity including renal failure (Åstrand et al., 2018; El Zahran et al., 2019). AM-2232 (3) is an analogue of the historically prevalent SCRA AM-2201 (4) described in a patent granted to Makriyannis and Deng (2001), and featuring a terminal nitrile group, that was previously detected in the German NPS market (Langer et al., 2014). The relatively greater CB1 binding affinity of AM-2232 (K i = 0.28 nM) compared to AM-2201 (K i = 1.0 nM) represents a possible motivation for the introduction of this motif in the case of CUMYL-4CN-BINACA (Makriyannis and Deng, 2001).
SGT-78 / Buy SGT-78 online .The cannabimimetic activity of several cumylamine-derived SCRAs has been described; they are potent CB1 receptor agonists in vitro and produce robust dose-dependent hypothermia in rodents (Asada et al., 2017; Longworth et al., 2017). Given multiple case reports of acute toxicity associated with CUMYL-4CN-BINACA, we sought to determine the hitherto uncharacterized pharmacological profile of this compound for direct comparison to its prevalent 5-fluoropentyl analogue. In the present study, we describe the binding affinity and functional activity of CUMYL-4CN-BINACA at human CB1 and CB2 receptors in vitro, as well as the cannabimimetic and pro-convulsant properties of this SCRA in mice .
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For radioligand binding, corrected counts were exported and analyzed utilizing Prism (GraphPad Software Inc., San Diego, CA). The “one-site fit K i” model was used, specifying radioligand K d as 1 nM for both CB1 and CB2. No other constraints were applied. Functional activity data were analyzed with Prism, using four-parameter nonlinear regression to fit concentration-response curves. A full CP 55,940 concentration response curve was completed every day, and a maximally effective concentration of CP 55,940 (1 µM) was included in every column of every plate to facilitate comparisons between experiments.
For in vivo biotelemetry, body temperature data were collated into 15-min bins using Dataquest A.R.T. software. Using Prism, each dose was compared to vehicle (or vehicle + CUMYL-4CN-BINACA for antagonist experiments) via an area under the curve (AUC) analysis over 3 h post-injection. Areas were analyzed using a one-way repeated-measures ANOVA with post hoc Dunnett’s contrasts.
For the behavioral observation experiments, mean Racine scores and locomotor activity were analyzed via a one-way ANOVAs, with Dunnett’s contrasts comparing the vehicle + 0.3 mg/kg CUMYL-4CN-BINACA condition to the remaining conditions.
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