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Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB(2) receptor inverse agonists.
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The cannabinoid CB(2) receptor is known to modulate osteoclast function by poorly understood mechanisms. Here, we report that the natural biphenyl neolignan 4'-O-methylhonokiol (MH) is a CB(2) receptor-selective antiosteoclastogenic lead structure (K(i) < 50 nM). Intriguingly, MH triggers a
Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes.
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ADB-CHMINACA (MAB-CHMINACA) is a new synthetic cannabinoid with high potency and many reported adverse events and fatalities. The drug is currently scheduled in several countries in Europe and the USA. Analytical methods need to be developed to confirm ADB-CHMINACA intake for clinical and forensic
Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist.
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Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously
Chain Substituted Cannabilactones with Selectivity for the CB2 Cannabinoid Receptor.
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In earlier work, we reported a novel class of CB2 selective ligands namely cannabilactones. These compounds carry a dimethylheptyl substituent at C3, which is typical for synthetic cannabinoids. In the current study with the focus on the pharmacophoric side chain at C3 we explored the effect of
Evaluation of the role of nicotinic acetylcholine receptor subtypes and cannabinoid system in the discriminative stimulus effects of nicotine in rats.
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Male Wistar rats were trained to discriminate (-)-nicotine (0.4 mg/kg) from saline under a two-lever, fixed-ratio 10 schedule of water reinforcement. During test sessions the following drugs were coadministered with saline (substitution studies) or nicotine (0.025-0.4 mg/kg; combination studies):
Acute myocardial infarction inhibits the neurogenic tachycardic and vasopressor response in rats via presynaptic cannabinoid type 1 receptor.
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The present study was carried out to examine whether acute experimental myocardial infarction affects the sympathetic transmission to vessels and the heart of pithed rats via a presynaptic mechanism and, if so, to check whether inhibitory presynaptic cannabinoid (CB) receptors and endocannabinoids
In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid.
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Metabolite profiling of novel psychoactive substances (NPS) is critical for documenting drug consumption. N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently
Cannabinoid CB1 and cholecystokinin CCK2 receptors modulate, in an opposing way, electrically evoked [3H]GABA efflux from rat cerebral cortex cell cultures: possible relevance for cortical GABA transmission and anxiety.
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The effects of treatments with cannabinoid (CB)(1) and cholecystokinin (CCK)(2) receptor agonists and antagonists, as well as compounds that enhance endocannabinoid signaling by inhibiting degradation, e.g., the fatty acid amide hydrolase inhibitor 3'-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate
Evidence for both inverse agonism at the cannabinoid CB1 receptor and the lack of an endogenous cannabinoid tone in the rat and guinea-pig isolated ileum myenteric plexus-longitudinal muscle preparation.
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OBJECTIVE
Cannabinoid receptor agonists reduce intestinal propulsion in rodents through the CB(1) receptor. In addition to its antagonistic activity at this receptor, rimonabant (N-(piperidino)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxyamide) alone augments intestinal
Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition.
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The endocannabinoid anandamide (AEA) plays a crucial role in emotional control, and inhibition of its degradation by the fatty acid amide hydrolase (FAAH) has a potent antianxiety effect. The mechanism by which the magnification of AEA activity reduces anxiety is still largely undetermined. By using
The endocannabinoid anandamide inhibits kinin B1 receptor sensitization through cannabinoid CB1 receptor stimulation in human umbilical vein.
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The possible inhibition of kinin B(1) receptor up-regulation by arachidonoylethanolamide (anandamide) was evaluated in isolated human umbilical vein. Anandamide and its metabolically stable analogue, R-N-(2-Hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (R-(+)-methanandamide), produced a
Separation and Identification of Isomeric and Structurally Related Synthetic Cannabinoids Using 2D Liquid Chromatography and High Resolution Mass Spectrometry.
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Novel psychoactive substances (NPS) are emerging drugs of abuse that are variations of existing compounds intended to cause a CNS psychotropic effect. Some NPS are so comparable in structure and physicochemical properties that they co-elute using traditional single column chromatographic techniques
HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in Mouse Brain Using Clean Screen FASt™ Column Extraction.
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A high-performance liquid chromatography tandem mass spectrometry method was developed for the detection and quantification of 6-methyl-3-(2-nitro-1-(thiophen-2-yl)propyl)-2-phenyl-1H-indole (ZCZ-011) using 2-phenylindole as the internal standard (ISTD). ZCZ-011 was synthesized as a possible
Synthetic cannabinoid BB-22 (QUCHIC): Human hepatocytes metabolism with liquid chromatography-high resolution mass spectrometry detection.
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Clandestine laboratories continue producing new synthetic cannabinoids that mimic and magnify natural cannabinoids effects to circumvent drug scheduling legislation. New synthetic cannabinoids are highly potent and responsible for many acute intoxications and deaths. Characterization of metabolic
Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor.
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In this work, we explored the molecular framework of the known CB1R allosteric modulator PSNCBAM-1 with the aim to generate new bioactive analogs and to deepen the structure-activity relationships of this type of compounds. In particular, the introduction of a NH group between the pyridine ring and
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