The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Luigi Cervo - One of the best experts on this subject based on the ideXlab platform.
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brain disposition of cis para methyl 4 methylaminorex cis 4 4 dmar and its potential metabolites after acute and chronic treatment in rats correlation with central behavioral effects
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Jacopo Lucchetti, Claudio Marcello Marzo, Alice Passoni, Federico Moro, Angelo Di Clemente, Renzo Bagnati, Marco Gobbi, Luigi CervoAbstract:para-Methyl-4-methylaminorex (4,4′-DMAR) is a Phenethylamine Derivative with psychostimulant activity whose abuse has been associated with several deaths and a wide range of adverse effects. We recently validated a high-performance liquid chromatography—tandem mass spectrometry method to measure the compound’s concentrations in plasma, and we applied it to describe the pharmacokinetic properties of 4,4′-DMAR after a single dose in rats. In this study, we investigated the brain disposition and metabolism of cis-4,4′-DMAR after intraperitoneal injection as well as its central behavioral effects. Locomotor activity increased after a single injection of 10 mg/kg, peaking at 2 hours and disappearing at 5 hours; in these conditions, brain absorption was very rapid, (tmax = 30–60 minutes) and large (brain-to-plasma ratio = 24); the half-life was approximately 50 minutes. After 14 daily doses, the compound’s effect on locomotor activity was greater (approximately 20% compared with the effect after the first dose), but not for pharmacokinetic reasons. Using high-resolution mass spectrometry, we also identified four metabolites of cis-4,4′-DMAR in the plasma and brain of treated rats. Semiquantitative analysis indicated low brain permeability and very low brain concentrations, suggesting that these metabolites do not contribute to central behavioral effects; however, the metabolite originating from oxidation of the para-methyl group (M2) persisted in the plasma longer and at higher concentrations than the parent molecule and could be used to evaluate drug intake in human consumers. Finally, we describe the rewarding effect of cis-4,4′-DMAR in the conditioning place preference test, suggesting a high risk of addiction in humans.
Nahoko Uchiyama - One of the best experts on this subject based on the ideXlab platform.
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a Phenethylamine Derivative 2 4 iodo 2 5 dimethoxyphenyl n 3 4 methylenedioxyphenyl methyl ethanamine 25i nb34md and a piperazine Derivative 1 3 4 difluoromethylenedioxybenzyl piperazine df mdbp newly detected in illicit products
Forensic Toxicology, 2016Co-Authors: Nahoko Uchiyama, Ruri Kikurahanajiri, Takashi HakamatsukaAbstract:Two new psychoactive substances (NPSs), a Phenethylamine Derivative 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(3,4-methylenedioxyphenyl)methyl]ethanamine (25I-NB34MD, 1) and a piperazine Derivative 1-(3,4-difluoromethylenedioxybenzyl)piperazine (DF-MDBP, 2), were identified in illicit products distributed from January to March 2015 in Japan. The identification was based on liquid chromatography–mass spectrometry (LC–MS), gas chromatography–mass spectrometry (GC–MS), high-resolution MS and nuclear magnetic resonance (NMR) analyses. Compound 1 has a 3,4-methylenedioxybenzyl moiety that is an analog of N-benzylmethoxy Derivatives of 2,5-dimethoxyPhenethylamines (“NBOMe”-compounds), e.g., 25I-NBOMe. Compound 2 is a difluoromethylenedioxy analog of the known designer drug 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). To our knowledge, this is the first report of compounds 1 and 2 detected as NPSs in illicit products. Although there is no chemical or pharmaceutical information for compound 1, a 2,3-methylenedioxy isomer of 1, 25I-NBMD, was reported to have a binding affinity for 5-HT2A receptor. In the GC–MS and LC–MS analyses, compound 1 (25I-NB34MD) showed spectra that are very similar to those of the isomer 25I-NBMD. The structure of compound 1 was determined here by an NMR analysis. Considering these results, we should be careful when analyzing NPSs in illicit products to prevent their misidentification as isomers of other NPSs. It is important to directly compare an unknown substance with an authentic substance by using multiple instruments such as GC–MS and LC–MS.
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A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a Phenethylamine Derivative N–OH-EDMA, and a cathinone Derivative dimethoxy-α-PHP, newly identified in illegal products
Forensic Toxicology, 2015Co-Authors: Nahoko Uchiyama, Yasuyuki Goda, Yoshihiko Shimokawa, Ruri Kikura-hanajiri, Yosuke Demizu, Takashi HakamatsukaAbstract:Six new psychoactive substances were identified together with two other substances (compounds 1–8) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4-fluorobenzyl)-N-(naphthalen-1-yl)-1H-indole-3-carboxamide, 2], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 (1). Two 2H-indazole isomers of synthetic cannabinoids, AB-CHMINACA 2H-indazole analog (3) and NNEI 2H-indazole analog (4), were newly identified with 1H-indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N-(naphthalen-1-yl) carbamate (5) and isobutyl 1-pentyl-1H-indazole-3-carboxylate (6) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1H-indazole. A Phenethylamine Derivative, N–OH-EDMA [N-hydroxy-3,4-ethylenedioxy-N-methylamphetamine, 7], and a cathinone Derivative, dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively.
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Identification of two new-type designer drugs, piperazine Derivative MT-45 (I-C6) and synthetic peptide Noopept (GVS-111), with synthetic cannabinoid A-834735, cathinone Derivative 4-methoxy-α-PVP, and Phenethylamine Derivative 4-methylbuphedrine fro
Forensic Toxicology, 2014Co-Authors: Nahoko Uchiyama, Maiko Kawamura, Ruri Kikura-hanajiri, Satoru Matsuda, Yukihiro GodaAbstract:We identified two new-type designer drugs, piperazine Derivative MT-45 [1-cyclohexyl-4-(1,2-diphenylethyl)piperazine, synonym: I-C6, 1 ] and synthetic peptide Noopept [ethyl 2-(1-(2-phenylacetyl)pyrrolidine-2-carboxamido)acetate, synonym: GVS-111, 2 ], in chemical and herbal products. MT-45 ( 1 ) was previously reported as an opiate-like analgesic substance, and Noopept ( 2 ) was reported to have nootropic (cognitive enhancer) activity. We also detected two synthetic cannabinoids, A-834735 ( 3 ) and QUPIC N -(5-fluoropentyl) analog (synonym: 5-fluoro-PB-22, 4 ), in the illegal products. A-834735 ( 3 ) was previously reported to act as an agonist at both cannabinoid CB_1 and CB_2 receptors. In addition, cathinone Derivative 4-methoxy-α-pyrrolidinovalerophenone (4-methoxy-α-PVP, 5 ) and Phenethylamine Derivative 4-methylbuphedrine ( 6 ) were newly detected with known cathinone Derivative 4-methylbuphedrone ( 7 ) in the products.
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ORIGINAL ARTICLE
2014Co-Authors: Nahoko Uchiyama, Yoshihiko Shimokawa, Ruri Kikura-hanajiri, Yosuke Demizu, Yukihiro Goda, Takashi HakamatsukaAbstract:A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a Phenethylamine Derivative N–OH-EDMA, and a cathinone Derivative dimethoxy-a-PHP, newly identified in illegal product
Takashi Hakamatsuka - One of the best experts on this subject based on the ideXlab platform.
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a Phenethylamine Derivative 2 4 iodo 2 5 dimethoxyphenyl n 3 4 methylenedioxyphenyl methyl ethanamine 25i nb34md and a piperazine Derivative 1 3 4 difluoromethylenedioxybenzyl piperazine df mdbp newly detected in illicit products
Forensic Toxicology, 2016Co-Authors: Nahoko Uchiyama, Ruri Kikurahanajiri, Takashi HakamatsukaAbstract:Two new psychoactive substances (NPSs), a Phenethylamine Derivative 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(3,4-methylenedioxyphenyl)methyl]ethanamine (25I-NB34MD, 1) and a piperazine Derivative 1-(3,4-difluoromethylenedioxybenzyl)piperazine (DF-MDBP, 2), were identified in illicit products distributed from January to March 2015 in Japan. The identification was based on liquid chromatography–mass spectrometry (LC–MS), gas chromatography–mass spectrometry (GC–MS), high-resolution MS and nuclear magnetic resonance (NMR) analyses. Compound 1 has a 3,4-methylenedioxybenzyl moiety that is an analog of N-benzylmethoxy Derivatives of 2,5-dimethoxyPhenethylamines (“NBOMe”-compounds), e.g., 25I-NBOMe. Compound 2 is a difluoromethylenedioxy analog of the known designer drug 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). To our knowledge, this is the first report of compounds 1 and 2 detected as NPSs in illicit products. Although there is no chemical or pharmaceutical information for compound 1, a 2,3-methylenedioxy isomer of 1, 25I-NBMD, was reported to have a binding affinity for 5-HT2A receptor. In the GC–MS and LC–MS analyses, compound 1 (25I-NB34MD) showed spectra that are very similar to those of the isomer 25I-NBMD. The structure of compound 1 was determined here by an NMR analysis. Considering these results, we should be careful when analyzing NPSs in illicit products to prevent their misidentification as isomers of other NPSs. It is important to directly compare an unknown substance with an authentic substance by using multiple instruments such as GC–MS and LC–MS.
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A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a Phenethylamine Derivative N–OH-EDMA, and a cathinone Derivative dimethoxy-α-PHP, newly identified in illegal products
Forensic Toxicology, 2015Co-Authors: Nahoko Uchiyama, Yasuyuki Goda, Yoshihiko Shimokawa, Ruri Kikura-hanajiri, Yosuke Demizu, Takashi HakamatsukaAbstract:Six new psychoactive substances were identified together with two other substances (compounds 1–8) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4-fluorobenzyl)-N-(naphthalen-1-yl)-1H-indole-3-carboxamide, 2], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 (1). Two 2H-indazole isomers of synthetic cannabinoids, AB-CHMINACA 2H-indazole analog (3) and NNEI 2H-indazole analog (4), were newly identified with 1H-indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N-(naphthalen-1-yl) carbamate (5) and isobutyl 1-pentyl-1H-indazole-3-carboxylate (6) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1H-indazole. A Phenethylamine Derivative, N–OH-EDMA [N-hydroxy-3,4-ethylenedioxy-N-methylamphetamine, 7], and a cathinone Derivative, dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively.
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ORIGINAL ARTICLE
2014Co-Authors: Nahoko Uchiyama, Yoshihiko Shimokawa, Ruri Kikura-hanajiri, Yosuke Demizu, Yukihiro Goda, Takashi HakamatsukaAbstract:A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a Phenethylamine Derivative N–OH-EDMA, and a cathinone Derivative dimethoxy-a-PHP, newly identified in illegal product
Jacopo Lucchetti - One of the best experts on this subject based on the ideXlab platform.
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brain disposition of cis para methyl 4 methylaminorex cis 4 4 dmar and its potential metabolites after acute and chronic treatment in rats correlation with central behavioral effects
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Jacopo Lucchetti, Claudio Marcello Marzo, Alice Passoni, Federico Moro, Angelo Di Clemente, Renzo Bagnati, Marco Gobbi, Luigi CervoAbstract:para-Methyl-4-methylaminorex (4,4′-DMAR) is a Phenethylamine Derivative with psychostimulant activity whose abuse has been associated with several deaths and a wide range of adverse effects. We recently validated a high-performance liquid chromatography—tandem mass spectrometry method to measure the compound’s concentrations in plasma, and we applied it to describe the pharmacokinetic properties of 4,4′-DMAR after a single dose in rats. In this study, we investigated the brain disposition and metabolism of cis-4,4′-DMAR after intraperitoneal injection as well as its central behavioral effects. Locomotor activity increased after a single injection of 10 mg/kg, peaking at 2 hours and disappearing at 5 hours; in these conditions, brain absorption was very rapid, (tmax = 30–60 minutes) and large (brain-to-plasma ratio = 24); the half-life was approximately 50 minutes. After 14 daily doses, the compound’s effect on locomotor activity was greater (approximately 20% compared with the effect after the first dose), but not for pharmacokinetic reasons. Using high-resolution mass spectrometry, we also identified four metabolites of cis-4,4′-DMAR in the plasma and brain of treated rats. Semiquantitative analysis indicated low brain permeability and very low brain concentrations, suggesting that these metabolites do not contribute to central behavioral effects; however, the metabolite originating from oxidation of the para-methyl group (M2) persisted in the plasma longer and at higher concentrations than the parent molecule and could be used to evaluate drug intake in human consumers. Finally, we describe the rewarding effect of cis-4,4′-DMAR in the conditioning place preference test, suggesting a high risk of addiction in humans.
Marco Gobbi - One of the best experts on this subject based on the ideXlab platform.
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brain disposition of cis para methyl 4 methylaminorex cis 4 4 dmar and its potential metabolites after acute and chronic treatment in rats correlation with central behavioral effects
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Jacopo Lucchetti, Claudio Marcello Marzo, Alice Passoni, Federico Moro, Angelo Di Clemente, Renzo Bagnati, Marco Gobbi, Luigi CervoAbstract:para-Methyl-4-methylaminorex (4,4′-DMAR) is a Phenethylamine Derivative with psychostimulant activity whose abuse has been associated with several deaths and a wide range of adverse effects. We recently validated a high-performance liquid chromatography—tandem mass spectrometry method to measure the compound’s concentrations in plasma, and we applied it to describe the pharmacokinetic properties of 4,4′-DMAR after a single dose in rats. In this study, we investigated the brain disposition and metabolism of cis-4,4′-DMAR after intraperitoneal injection as well as its central behavioral effects. Locomotor activity increased after a single injection of 10 mg/kg, peaking at 2 hours and disappearing at 5 hours; in these conditions, brain absorption was very rapid, (tmax = 30–60 minutes) and large (brain-to-plasma ratio = 24); the half-life was approximately 50 minutes. After 14 daily doses, the compound’s effect on locomotor activity was greater (approximately 20% compared with the effect after the first dose), but not for pharmacokinetic reasons. Using high-resolution mass spectrometry, we also identified four metabolites of cis-4,4′-DMAR in the plasma and brain of treated rats. Semiquantitative analysis indicated low brain permeability and very low brain concentrations, suggesting that these metabolites do not contribute to central behavioral effects; however, the metabolite originating from oxidation of the para-methyl group (M2) persisted in the plasma longer and at higher concentrations than the parent molecule and could be used to evaluate drug intake in human consumers. Finally, we describe the rewarding effect of cis-4,4′-DMAR in the conditioning place preference test, suggesting a high risk of addiction in humans.