共查询到20条相似文献,搜索用时 31 毫秒
1.
A new synthetic cannabinoid, [1-(tetrahydropyran-4-ylmethyl)-1 H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone, was identified in several resinous samples seized by law enforcement officers in Poland. Its identification was based on liquid chromatography–electrospray ionization–quadrupole time-of-flight–mass spectrometry, gas chromatography–electron ionization–mass spectrometry, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, and Fourier-transform infrared spectroscopy. The reported substance was first developed by Abbott Laboratories and patented under the name “A-834,735”. It is a potent agonist of both CB 1 and CB 2 receptors. Although A-834,735 shows moderate selectivity to CB 2 receptor, it exhibits a CB 1 affinity similar to that of ? 9-tetrahydrocannabinol. The drug has recently become available in online shops. To our knowledge, this is the first report to disclose a synthetic cannabinoid containing a (tetrahydropyran-4-yl)methyl structure in products seized from the drug market. 相似文献
2.
We encountered during our investigation a case of herbal drug products commercially available in the Tokyo metropolitan area in 2014, in which a small unknown peak was detected, along with the intense peak of FUB-144, by liquid chromatography–ultraviolet detection. The present study was conducted to identify and clarify the pharmacological characteristics of the compound present in this small peak. We isolated a compound using a silica gel column from the peak, which was then identified to have a molecular weight of 241 Da by liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. The accurate mass measurement suggested an elementary composition of C 16H 19NO. Using these mass data together with those obtained by the nuclear magnetic resonance analysis, the compound was finally identified as (1 H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (despentyl-UR-144; DP-UR-144). In addition, this compound was revealed to have affinities for cannabinoid receptors CB 1 and CB 2 with EC 50s of 2.36 × 10 ?6 and 2.79 × 10 ?8 M, respectively. To our knowledge, there is no information in the scientific literature on structural or pharmacological properties of this chemical. These results suggest that the components present in small amounts can contribute to the effects of a major component in their mother product, if they have sufficient pharmacological activities, and, therefore, even such small amounts of components should be precisely characterized and well evaluated to control illegal and potentially illegal drug products. 相似文献
3.
Six cannabimimetic indoles have been identified as adulterants in herbal or chemical products being sold illegally in Japan,
with four of the compounds being new as adulterants to our knowledge. The identifications were based on analyses using gas
chromatography–mass spectrometry, liquid chromatography–mass spectrometry, high-resolution mass spectrometry, and nuclear
magnetic resonance spectroscopy. The first two compounds were identified as phenylacetyl indoles JWH-251 (2-(2-methylphenyl)-1-(1-pentyl-1 H-indol-3-yl)ethanone; 1) and its demethyl-methoxylated analog JWH-250 (2-(2-methoxyphenyl)-1-(1-pentyl-1 H-indol-3-yl)ethanone; 2). Compound 2 was identical to that found as an adulterant in the UK and in Germany in 2009. The third compound was naphthoylindole JWH-081
(1-(4-methoxynaphthalenyl)-(1-pentyl-1 H-indol-3-yl)methanone; 3), and the fourth was JWH-073 (1-naphthalenyl(1-butyl-1 H-indol-3-yl)methanone; 4), which had been identified as an adulterant in our previous study. Two additional compounds were JWH-015 (1-naphthalenyl(2-methyl-1-propyl-1 H-indol-3-yl)methanone; 5) and JWH-200 (1-naphthalenyl(1-(2-(4-morpholinyl)ethyl)-1 H-indol-3-yl)methanone; 6). Compounds 1– 4 and 6 were reported to be synthetic cannabinoids with selective affinity for cannabinoid CB 1 receptors, while compound 5 was reported to be a selective CB 2 receptor agonist causing immunosuppressive effects without psychotropic affects. One product contained both CB 1 and CB 2 receptor agonists in our collection. Quantitative analyses of the six cannabimimetic compounds in 20 products revealed that
there was large variation in concentrations of the detected compounds among products; for herbal cutting products, the total
amounts of these cannabinoids ranged from 26 to 100 mg. 相似文献
4.
In recent years, many synthetic cannabinoid (CB) receptor agonists have appeared on the market as constituents of herbal incense mixtures known as “spice”. Contrary to the declared use, they are perorally consumed as a replacement for marijuana to get “high”. In many cases, detailed information on the physicochemical and pharmacological properties of the synthetic compounds found in spice preparations is lacking. We have now evaluated a large series of heterocyclic compounds, 1,3-disubstituted indole and 2-azaindole derivatives known or assumed to be CB 1 receptor agonists, many of which have previously been identified in forensic samples. The mainly observed structural variations to circumvent restriction by law were bioisosteric exchanges of functional groups in known CB 1 agonists. We analyzed the structure-activity relationships of compounds at human CB 1 and CB 2 receptors based on affinities obtained in radioligand binding studies, and determined their efficacy in cAMP accumulation assays. Moreover, we investigated the activities of the compounds at the orphan G protein-coupled receptors GPR18 and GPR55 both of which are known to interact with cannabinoids. Most of the investigated compounds behaved as potent full agonists of CB 1 and CB 2 receptors with affinities in the low nanomolar to subnanomolar concentration range. Some compounds were moderately potent GPR55 antagonists, while none interacted with GPR18. Most derivatives were predicted to cross the blood–brain barrier as determined by bioinformatics tools. These data are useful for assessing synthetic cannabinoids and will be helpful for predicting pharmacological properties of novel compounds that appear on the illicit drug market. 相似文献
5.
PurposeSome of the synthetic cannabinoids, often found in recreational drugs of the herbal form, reportedly induce a generalized seizure in drug abusers immediately after smoking. However, it is still unclear what elicits the sensorimotor responses, particularly in the case of hyperreflexia or excitatory behavior during the synthetic cannabinoid exposure. The purpose of this study was to explore the mechanism underlying the hyperreflexia induced by smoke intoxication of XLR-11 [(1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone]. MethodsLocomotor activity and body temperature of mice were measured using an implanted Nano-Tag device. The intensity of catalepsy was determined by the bar test. The extracellular dopamine levels in the nucleus accumbens and glutamate levels in the hippocampus were measured by in vivo microdialysis using electrochemical detector-coupled high-performance liquid chromatography and by in vivo enzyme-based biosensor method, respectively. ResultsMice exposed to the smoke of XLR-11 exhibited hyperreflexia at the very early phase, followed by hypothermia and catalepsy. The XLR-11 smoke contained XLR-11 and XLR-11 degradant at a ratio of approximately 1:25. Mice treated intraperitoneally with XLR-11 degradant at a dose comparable to the smoke inhalation experiment showed a hyperreflexic effect immediately after the treatment, but XLR-11 showed no such effect. The effects of XLR-11 degradant were significantly suppressed by pretreatment with AM-251, a CB1 receptor antagonist. Extracellular dopamine and glutamate levels showed no evidence of involvement in the XLR-11 degradant-induced hyperreflexia; on the other hand gabapentin, a GABAergic antiepileptic, significantly suppressed the enhanced locomotor activity. ConclusionsThe hyperreflexic effect of XLR-11 degradant is mediated by the CB1 receptor and possibly by GABAergic function. 相似文献
6.
1-Pentyl-3-(4-methyl-1-naphthoyl)indole (JWH-122) is an agonist of the cannabinoid receptors CB 1 and CB 2. In this study, the phase I and phase II metabolisms of JWH-122 were investigated using two models. In vitro studies using incubations of JWH-122 with human liver microsomes were performed to obtain metabolites of the drug at the initial step; 11 classes of metabolites were found and analyzed by liquid chromatography–mass spectrometry (LC–MS) and liquid chromatography–tandem mass spectrometry (LC–MS–MS). Hydroxylation(s) on the naphthalene moiety and/or the indole moiety of the molecule took place as such or in combination with dehydrogenation or cleavage of the N-pentyl side chain. Furthermore, dihydrodiol metabolites were formed probably via epoxide formation on the naphthalene moiety, irrespective of the combination with hydroxylation(s). A metabolite carrying a carboxyl group on the N-pentyl side chain was also detected. As the second step of the study, in vivo experiments using chimeric mice were performed; the mice were orally administered JWH-122, and their urine samples were collected, subjected to enzymatic hydrolysis, and analyzed by LC–MS and LC–MS–MS. The urine samples without hydrolysis were also analyzed for their molecular formulae in the conjugated forms by LC–high resolution MS. The in vivo model using chimeric mice confirmed most metabolite classes and clarified the phase II metabolism of JWH-122. It was concluded that all metabolites formed in vivo were excreted conjugated as glucuronide or sulfate, with conjugation rates above 50 %. 相似文献
7.
The rapid increase in the number of new psychoactive substances and their abuse is the most recent drug abuse issue worldwide. Although abuse of synthetic cannabinoids is highly restricted in South Korea, the rapid increase in the number of new substances is forcing the legal regulation authority to continuously improve the drug regulation act. As a result of drug screening by the National Forensic Service from 2009 to June 2013, 26 species of synthetic cannabinoids were identified in materials seized mainly by the Police Agency and the Prosecutor’s Office in South Korea. One of the most remarkable trends in synthetic cannabinoids is the increase in halogenated derivatives and new substances, including UR-144 and A-836,339 originally developed as analgesics by Abbott Laboratories. The N-pentyl fluorinated analog of UR-144 (XLR-11) has become the most frequently found synthetic cannabinoid in 2013 since its first appearance in 2012, whereas abuse of A-836,339 analogs has been little reported despite their abuse potential. Until early 2011, nicotine was the most frequently found active coingredient with synthetic cannabinoids. However, various psychoactive substances such as Δ 9-tetrahydrocannabinol, α-pyrrolidinobutiophenone, α-pyrrolidinovalerothiophenone, and N, N-diallyl-5-methoxytryptamine have often been found as coingredients in herbal highs since late 2011. These coingredients should also be systematically regulated, because they can cause unexpected side effects. It is suggested that authorities in different countries share information about synthetic cannabinoids and their coingredients. 相似文献
8.
Two new cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1 H-indazole-3-carboxamide (AB-PINACA, 1) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1 H-indazole-3-carboxamide (AB-FUBINACA, 2), have been identified as designer drugs in illegal products. These identifications were based on liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy. Because there have been neither chemical nor pharmacological data about compound 1 until now, this is the first report of this compound. Compound 2 was reported as a potent cannabinoid CB 1 receptor modulator when synthesized by Pfizer in 2009; but this is the first report of its detection in illegal products. 相似文献
9.
As a part of the work conducted in our laboratory, we encountered a case in which new chemical compound was contained in a certain product. This compound was found to have a molecular weight of 310 Da by liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. Accurate mass spectrometry measurements showed that the compound had an elemental composition of C 16H 26N 2O 2S. Using these mass data together with those obtained by nuclear magnetic resonance analysis and X-ray crystallographic analysis, this compound was identified as N-[3-(2-methoxyethyl)-4,5-dimethyl-2(3 H)-thiazolylidene]-2,2,3,3-tetramethylcyclopropanecarboxamide, which was reported in 2009 and named A-836339. It was described as a thiazol derivative and a selective agonist of G-protein-coupled cannabinoid receptor CB 2. This is the first report to identify this compound in a dubious product. 相似文献
10.
1-Pentyl- N-(2-phenylpropan-2-yl)-1 H-indazole-3-carboxamide (CUMYL-PINACA) is a carboxamide-type synthetic cannabinoid comprising a cumylamine moiety. Recently, the detection of CUMYL-PINACA and some analogs in illicit drug products has been reported by the European Monitoring Centre for Drugs and Drug Addiction. In this study, we synthesized seven cumyl carboxamide-type synthetic cannabinoids (CUMYL-PINACA, CUMYL-5F-PINACA, CUMYL-PICA, CUMYL-5F-PICA, CUMYL-THPINACA, CUMYL-BICA, and CUMYL-5F-P7AICA) and evaluated their activities as CB 1 and CB 2 receptor agonists. We also showed the analytical characterization of these compounds using gas chromatography–electron ionization-mass spectrometry. All of the evaluated compounds exhibited moderate to strong activities as agonists acting on both CB 1 and CB 2 receptors with EC 50 values in the range of 8.1 × 10 ?10–7.8 × 10 ?7 mol/L for CB 1 and from 2.5 × 10 ?10 to 9.1 × 10 ?6 mol/L for CB 2. The EC 50 data presented will be helpful to understand the effects of these compounds in the forensic cases. Furthermore, other new cumyl carboxamide-type synthetic cannabinoids, which will be potentially distributed in the future, will probably have the activities as agonists acting on both CB 1 and CB 2 receptors. 相似文献
11.
PurposeThree synthetic carboxamide-type cannabinoids (5F-MDMB-PICA, 5F-EMB-PINACA, and AMB-CHMICA) were evaluated in terms of their in vitro activities at the cannabinoid receptors CB1 and CB2 and in vivo biological effects when smoking the synthetic cannabinoids to assess their biological effects. Methods[35S]Guanosine-5′-O-(3-thio)-triphosphate binding assays were performed to investigate the half maximal effective concentration values of the test compounds at the CB1 and CB2 receptors. Additionally, the biological effects were evaluated by observing and scoring the behavior of mice with equipment in which they inhaled smoke from a herbal mixture containing the test compounds. ResultsAll three synthetic cannabinoids tested in this study activated the CB1 and CB2 receptors in vitro. 5F-MDMB-PICA showed less than 1 nM of the half maximal effective concentration value for both receptors. Therefore, it was suggested that 5F-MDMB-PICA was the strongest CB1 and CB2 receptor agonist in comparison with synthetic cannabinoids evaluated in the past. The degree of the various biological effects, specifically passivity, spontaneous activity, abnormal gait, abnormal position, and grip strength, when smoking the synthetic cannabinoids corresponded to the functional activity at the CB1 receptor. However, some biological effects differed between 5F-MDMB-PICA and 5F-MDMB-PINACA, used as a positive control, and AMB-CHMICA induced some biological effects in contrast to the other tested synthetic cannabinoids. ConclusionThis study provides information regarding the biological effects when smoking synthetic cannabinoids from the functional activities at the CB1 and CB2 receptors, considering their way of inhalation and thermal degradation. 相似文献
12.
A cannabimimetic indole has been identified as a new adulterant in a herbal product being sold illegally in Japan for its
expected narcotic effect. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry analyses indicated
that the product contained two major compounds. One was identified as a cannabinoid analog (1 RS,3 SR)-3-[4-(1,1-dimethyloctyl)-2-hydroxyphenyl]cyclohexan-1-ol ( 1) by direct comparison with the authentic compound, which we reported previously. The other compound ( 2) showed a molecular weight of 341 daltons, and accurate mass spectral measurements showed its elemental composition to be
C 24H 23NO. Both mass and nuclear magnetic resonance spectrometric data revealed that 2 was 1-pentyl-3-(1-naphthoyl)indole [or naphthalen-1-yl-(1-pentylindol-3-yl)methanone] being identical to JWH-018, which was
synthesized by Wiley and coworkers in 1998. This compound was reported as a potent cannabinoid receptor agonist possessing
a pharmacological cannabimimetic activity. 相似文献
13.
PurposeIn the present study we characterized a series of synthetic cannabinoids containing various heterocyclic scaffolds that had been identified as constituents of “Spice”, a preparation sold on the illicit drug market. All compounds were further investigated as potential ligands of the orphan receptors GPR18 and GPR55 that interact with some cannabinoids.MethodsThe compounds were studied in radioligand binding assays to determine their affinity for human cannabinoid CB1 and CB2 receptors expressed in CHO cells, and in cAMP accumulation assays to study their functionality.ResultsStructure-activity relationships were analyzed. The most potent CB1 receptor agonist of the present series MDMB-FUBINACA (12) (Ki?=?98.5 pM) was docked into the human CB1 receptor structure, and a plausible binding mode was identified showing high similarity with that of the co-crystallized THC derivatives. MDMB-CHMCZCA (41) displayed a unique profile acting as a full agonist at the CB1 receptor subtype, but blocking the CB2 receptor completely. Only a few weakly potent antagonists of GPR18 and GPR55 were identified, and thus all compounds showed high CB receptor selectivity, mostly interacting with both subtypes, CB1 and CB2.ConclusionsThese results will be useful to assess the compounds’ toxicological risks and to guide legislation. Further studies on 41 are warranted. 相似文献
14.
In our survey of designer drugs in the Japanese market, a cannabimimetic indole was identified as a new active compound in a herbal product. The structure of this compound was elucidated by liquid chromatography–photodiode array–mass spectrometry (LC–PDA–MS), gas chromatography–mass spectrometry (GC–MS), high-resolution MS, and nuclear magnetic resonance (NMR) analyses. The compound was finally identified as (4-ethyl-1-naphthalenyl)(2-methyl-1-pentyl-1 H-indol-3-yl)methanone (JWH-213), an indole-based cannabinoid receptor ligand. To our knowledge, this is the first finding of JWH-213 as a designer drug in a herbal product. The quantitative LC–PDA analysis showed that the JWH-213 content in the product was 252 mg/pack. 相似文献
15.
IntroductionThe type 2 cannabinoid (CB 2) receptor is part of the endocannabinoid system and has been suggested as a mediator of several central and peripheral inflammatory processes. Imaging of the CB 2 receptor has been unsuccessful so far. We synthesized and evaluated a carbon-11- and a fluorine-18-labeled 2-oxoquinoline derivative as new PET tracers with high specificity and affinity for the CB 2 receptor. MethodsTwo 2-oxoquinoline derivatives were synthesized and radiolabeled with either carbon-11 or fluorine-18. Their affinity and selectivity for the human CB 2 receptor were determined. Biological evaluation was done by biodistribution, radiometabolite and autoradiography studies in mice. ResultsIn vitro studies showed that both compounds are high affinity CB 2-specific inverse agonists. Biodistribution study of the tracers in mice showed a high in vivo initial brain uptake and fast brain washout, in accordance with the low CB 2 receptor expression levels in normal brain. A persistently high in vivo binding to the spleen was observed, which was inhibited by pretreatment with two structurally unrelated CB 2 selective inverse agonists. In vitro autoradiography studies with the radioligands confirmed CB 2-specific binding to the mouse spleen. ConclusionWe synthesized two novel CB 2 receptor PET tracers that show high affinity/selectivity for CB 2 receptors. Both tracers show favourable characteristics as radioligands for central and peripheral in vivo visualization of the CB 2 receptor and are promising candidates for primate and human CB 2 PET imaging. 相似文献
16.
We identified two new-type cannabimimetic quinolinyl carboxylates, quinolin-8-yl 1-pentyl-(1 H-indole)-3-carboxylate (QUPIC, 1) and quinolin-8-yl 1-(cyclohexylmethyl)-1 H-indole-3-carboxylate (QUCHIC, 2); and two new cannabimimetic carboxamide derivatives, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1 H-indazole-3-carboxamide (ADB-FUBINACA, 3) and N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl-1 H-indole-3-carboxamide (ADBICA, 4), as designer drugs in illegal products. Compound 3 was reported to have a potent affinity for cannabinoid CB 1 receptor by Pfizer in 2009, but this is the first report of its detection in illegal products. No chemical or pharmacological data for compounds 1, 2, and 4 have appeared until now, making this the first report on these compounds. We also detected synthetic cannabinoids, APICA N-(5-fluoropentyl) analog ( 5), APINACA N-(5-fluoropentyl) analog ( 6), UR-144 N-(5-chloropentyl) analog ( 7), JWH-122 N-(5-chloropentyl) analog ( 8), and AM-2201 4-methoxynaphthyl analog (4-MeO-AM-2201, 9) herein as newly distributed designer drugs in Japan. It is of interest that compounds 1 and 2 were detected with their synthetic component, 8-quinolinol ( 10). A stimulant thiophene analog, α-pyrrolidinovalerothiophenone (α-PVT, 11), and an opioid receptor agonist, 3,4-dichloro- N-([1-(dimethylamino)cyclohexyl]methyl)benzamide (AH-7921, 12), were also detected as new types of designer drugs coexisting with several synthetic cannabinoids and cathinone derivatives in illegal products. 相似文献
17.
IntroductionThe cannabinoid receptor type 2 (CB 2) is an important target for development of drugs and imaging agents for diseases, such as neuroinflammation, neurodegeneration and cancer. Recently, we reported synthesis and results of in vitro receptor binding of a focused library of fluorinated 2-oxoquinoline derivatives as CB 2 receptor ligands. Some of the compounds demonstrated to be good CB 2-specific ligands with Ki values in the nanomolar to subnanomolar concentrations; therefore, we pursued the development of their 18F-labeled analogues that should be useful for positron emission tomography (PET) imaging of CB 2 receptor expression. Here, we report the radiosynthesis of two 18F-labeled 2-oxoquinoline derivatives and the preliminary in vitro and ex vivo evaluation of one compound as a CB 2-specific radioligand. Methods4-[ 18F]fluorobenzyl amine [ 18F]- 3 was prepared by radiofluorination of 4-cyano- N,N,N-trimethylanilinium triflate salt followed by reduction with LiAlH 4 and then coupled with acid chlorides 11 and 12 to afford [ 18F]- 13 and [ 18F]- 14. In vitro CB 2 receptor binding assay was performed using U87 cells transduced with CB 2 and CB 1 receptor. Ex vivo autoradiography was performed with [ 18F]- 14 on spleen and on CB 2- and CB 1-expressing and wild-type U87 subcutaneous tumors grown in mice. ResultsThe radiochemical yields of [ 18F]- 13 and [ 18F]- 14 were 10%–15.0% with an average of 12% ( n=10); radiochemical purity was >99% with specific activity 1200 mCi/μmol. The dissociation constant Kd for [ 18F]- 14 was 3.4 nM. Ex vivo autoradiography showed accumulation of [ 18F]- 14 in the CB 2-expressing tumor. ConclusionTwo new [ 18F]-labeled CB 2 ligands have been synthesized. Compound [ 18F]- 14 appears to be a potential PET imaging agent for the assessment of CB 2 receptor expression; however, poor solubility restrain its use in vivo. 相似文献
18.
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. 相似文献
19.
Traffic police brought five dubious herbal product packages to our laboratory for toxicological analysis. These products usually contain one or multiple kinds of synthetic cannabinoids. In one of the packages, we identified the coexistence of a new type of dubious drug (diphenidine) with the synthetic cannabinoid 5-fluoro-AB-PINACA. Conclusive identification was performed by comparison of the mass spectra of the test herb extracts with those of the reference standards of diphenidine and 5-fluoro-AB-PINACA by both gas chromatography–mass spectrometry (GC–MS) and electrospray ionization–tandem mass spectrometry. Both mass spectra of the test extracts coincided with those of the reference standards for each MS method. Diphenidine and 5-fluoro-AB-PINACA were quantitated in the herbal product by GC–MS using selected ion monitoring and the standard addition method. The content of diphenidine in the herbal product was as high as 289 ± 23.2 mg/g ( n = 5); that of 5-fluoro-AB-PINACA was 55.5 ± 5.8 mg/g ( n = 3). Diphenidine is known as an N-methyl- d-aspartate receptor channel blocker. Although its human toxicity has not been studied, it is likely to have severe psychotropic action in humans. The very high content of diphenidine in the present herbal package should prompt law enforcement agencies to be aware of the potential harmful effects of diphenidine itself and also when consumed in combination with other drugs of abuse. 相似文献
20.
Recently, carboxamide-type synthetic cannabinoids have been distributed globally as new psychoactive substances (NPS). Some of these compounds possess asymmetric carbon, which is derived from an amide moiety composed of amino acid derivatives (i.e., amides or esters of amino acids). In this study, we synthesized both enantiomers of synthetic cannabinoids, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(2-fluorobenzyl)-1 H-indazole-3-carboxamide (AB-FUBINACA 2-fluorobenzyl isomer), N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(cyclohexylmethyl)-1 H-indazole-3-carboxamide (APP-CHMINACA), ethyl [1-(5-fluoropentyl)-1 H-indazole-3-carbonyl]valinate (5F-EMB-PINACA), ethyl [1-(4-fluorobenzyl)-1 H-indazole-3-carbonyl]valinate (EMB-FUBINACA), and methyl 2-[1-(4-fluorobenzyl)-1 H-indole-3-carboxamido]-3,3-dimethylbutanoate (MDMB-FUBICA), which were reported as NPS found in Europe from 2014 to 2015, to evaluate their activities as CB 1/CB 2 receptor agonists. With the exception of ( R) MDMB-FUBICA, all of the tested enantiomers were assumed to be agonists of both CB 1 and CB 2 receptors, and the EC 50 values of the ( S)-enantiomers for the CB 1 receptors were about five times lower than those of ( R)-enantiomers. ( R) MDMB-FUBICA was shown to function as an agonist of the CB 2 receptor, but lacks CB 1 receptor activity. To the best of our knowledge, this is the first report to show that the ( R)-enantiomers of the carboxamide-type synthetic cannabinoids have the potency to activate CB 1 and CB 2 receptors. The findings presented here shed light on the pharmacological properties of these carboxamide-type synthetic cannabinoids in forensic cases. 相似文献
|