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PubMed Journals Articles About "Activation Cannabinoid Type Receptor Novel Indazole Derivative Normalizes" RSS

07:26 EST 23rd January 2019 | BioPortfolio

Activation Cannabinoid Type Receptor Novel Indazole Derivative Normalizes PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Activation Cannabinoid Type Receptor Novel Indazole Derivative Normalizes articles that have been published worldwide.

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Showing "Activation Cannabinoid Type Receptor Novel Indazole Derivative Normalizes" PubMed Articles 1–25 of 24,000+

Identification and characterization of an indazole-3-carboxamide class synthetic cannabinoid: 2-1-(cyclohexylmethyl)-1H-indazole-3-carboxamido-3,3-dimethylbutanoic acid (DMBA-CHMINACA).

Illicit psychoactive substances have threatened public health worldwide. An active metabolite of ADB-CHMINACA and MDMB-CHMINACA was identified for the first time in a powder-type product found in an airmail package. The structure of compound 1 was elucidated by a combination of gas chromatography-mass spectrometry (GC-MS), liquid chromatography-high resolution mass spectrometry (LC-HRMS), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Compound 1 was proven to be an analogue o...


Effect of cannabinoid receptor agonists on isolated rat atria.

Cannabinoid CB2 receptor agonists are under investigation for clinical use. At the same time, synthetic cannabinoids have been implicated in a number of deaths. One cause of death is thought to be cardiac arrest subsequent to extreme tachycardia. Central mechanisms are thought to play a role in this, with CB1 but not CB2 receptors thought to mediate central effects. However, the direct effects on cannabinoids on the heart is less well understood. We therefore tested the effects of cannabinoids on isolated r...

Emerging strategies targeting cb cannabinoid receptor: biased agonism and allosterism.

During these last years, the CB cannabinoid receptor has emerged as a potential anti-inflammatory target in diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, ischemic stroke, autoimmune diseases, osteoporosis, and cancer. However, the development of clinically useful CB agonists reveals to be very challenging. Allosterism and biased-signaling mechanisms at CB receptor may offer new avenues for the development of improved CB receptor-targeted therapies. Although there ...


The Chemistry and Pharmacology of Synthetic Cannabinoid Receptor Agonists as New Psychoactive Substances: Origins.

Synthetic cannabinoid receptor agonists (SCRAs) have proliferated as new psychoactive substances (NPS) over the past decade. Relative to other classes of NPS, SCRAs are structurally heterogeneous; however, most SCRAs act as potent, high-efficacy agonists of cannabinoid type 1 and type 2 receptors (CB and CB, respectively). Characterization of the pharmacology and toxicology of these substances is hindered by the dynamic nature of the SCRA marketplace. Beyond basic pharmacological profiling at CB and CB rece...

Synthetic cannabinoid hydroxypentyl metabolites retain efficacy at human cannabinoid receptors.

Synthetic cannabinoids (SCs) are novel psychoactive substances that are easily acquired, widely abused as a substitute for cannabis, and associated with cardiotoxicity and seizures. While the structures of these compounds are based upon scaffolds with known affinity and efficacy at the human cannabinoid type-1 receptor (hCB), upon ingestion or inhalation they can be metabolized to multiple chemical entities of unknown pharmacological activity. A large proportion of these metabolites are hydroxylated on the ...

Endocannabinoid receptor CB2R is significantly expressed in aspirin-exacerbated respiratory disease: a pilot study.

The endocannabinoid system represents a highly conserved, innate signaling network with direct and indirect control of eicosanoid-mediated inflammation. Activation of the type 2 cannabinoid receptor (CB2R) leads to decreased type 2 inflammation and reduced production of arachidonic acid (AA). Given that altered AA metabolism is associated with aspirin-exacerbated respiratory disease (AERD), we hypothesized that expression of the CB2R gene CNR2 is increased in AERD.

Progress in Brain Cannabinoid CB Receptor Research: From Genes to Behavior.

The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, bu...

Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history.

Cannabis sativa L. (C. sativa) is an annual dioecious plant, which shares its origins with the inception of the first agricultural human societies in Asia. Over the course of time different parts of the plant have been utilized for therapeutic and recreational purposes, for instance, extraction of healing oils from seed, or the use of inflorescences for their psychoactive effects. The key psychoactive constituent in C. sativa is called Δ-9-tetrahydrocannabinol (D9-THC). The endocannabinoid system seems to ...

Cannabinoid receptor types 1 and 2 and peroxisome proliferator-activated receptor-α: distribution in the skin of clinically healthy cats and cats with hypersensitivity dermatitis.

Cannabinoid receptors and peroxisome proliferator-activated receptor-alpha (PPAR-α) are gaining recognition as potential therapeutic targets for the treatment of skin disorders.

The tamoxifen derivative ridaifen-B is a high affinity selective CB receptor inverse agonist exhibiting anti-inflammatory and anti-osteoclastogenic effects.

Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER...

A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice.

The overactivity of cannabinoid 1 receptor (CB1R) is associated with obesity and type 2 diabetes. First-generation CB1R antagonists, such as rimonabant, offered therapeutic advantages for the control of obesity and related metabolic abnormalities, but their therapeutic potential was limited by undesirable neuropsychiatric side effects. Here, we evaluated AJ5012 as a novel potent peripheral CB1R antagonist and, using this antagonist, investigated the role of peripheral CB1R on adipose tissue inflammation in ...

FFMPEP-d PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease.

Contradictory findings on the role of the type 1 cannabinoid receptor (CBR) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CBR brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CBR, [F]FMPEP-d. APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CBR immunohistochemistry with additional mice...

Brain-Derived Neurotrophic Factor (BDNF) Role in Cannabinoid-Mediated Neurogenesis.

The adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown. We now used SVZ and DG neurosphere cultures from early (P1-3) postnatal rats to study the CB1R and CB2R crosstalk with BDNF in...

Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.

Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer. In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer.

Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis.

In sterile neuroinflammation, a pathological role is proposed for microglia, whereas in viral encephalitis, their function is not entirely clear. Many viruses exploit the odorant system and enter the CNS via the olfactory bulb (OB). Upon intranasal vesicular stomatitis virus instillation, we show an accumulation of activated microglia and monocytes in the OB. Depletion of microglia during encephalitis results in enhanced virus spread and increased lethality. Activation, proliferation, and accumulation of m...

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system.

The endocannabinoid system (ECS) exerts a modulatory effect of important functions such as neurotransmission, glial activation, oxidative stress, or protein homeostasis. Dysregulation of these cellular processes is a common neuropathological hallmark in aging and in neurodegenerative diseases of the central nervous system (CNS). The broad spectrum of actions of cannabinoids allows targeting different aspects of these multifactorial diseases. In this review, we examine the therapeutic potential of the ECS fo...

Adolescent Δ-Tetrahydrocannabinol Exposure and Astrocyte-Specific Genetic Vulnerability Converge on Nuclear Factor-κB-Cyclooxygenase-2 Signaling to Impair Memory in Adulthood.

Although several studies have linked adolescent cannabis use to long-term cognitive dysfunction, there are negative reports as well. The fact that not all users develop cognitive impairment suggests a genetic vulnerability to adverse effects of cannabis, which are attributed to action of Δ9-tetrahydrocannabinol (Δ-THC), a cannabis constituent and partial agonist of brain cannabinoid receptor 1. As both neurons and glial cells express cannabinoid receptor 1, genetic vulnerability could influence Δ-THC-ind...

Expression and Preparation of a G-Protein-Coupled Cannabinoid Receptor CB for NMR Structural Studies.

Cannabinoid receptor type II, or CB , is an integral membrane protein that belongs to a large class of G-protein-coupled receptors (GPCR)s. CB is a part of the endocannabinoid system, which plays an important role in the regulation of immune response, inflammation, and pain. Information about the structure and function of CB is essential for the development of specific ligands targeting this receptor. We present here a methodology for recombinant expression of CB and its stable isotope labeling, purificatio...

The endocannabinoid 2-arachidonoylglycerol regulates oligodendrocyte progenitor cell migration.

While the endocannabinoid 2-arachidonoylglycerol (2-AG) is thought to enhance the proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) in vitro, less is known about how endogenous 2-AG may influence the migration of these cells. When we assessed this in Agarose drop and Boyden chemotaxis chamber assays, inhibiting the sn-1-diacylglycerol lipases α and β (DAGLs) that are responsible for 2-AG synthesis significantly reduced the migration of OPCs stimulated by platelet-derived growth ...

Inflammation and oxidative stress are key mediators in AKB48-induced neurotoxicity in vitro.

Synthetic cannabinoids were introduced into market in early 2000s; since these "legal highs" are dramatically popular among youth, it becomes a deadly problem. Synthetic cannabinoids have high affinity to cannabinoid receptors; leading to various clinical symptoms. AKB48 (Apinaca) has been classified as a third-generation synthetic cannabinoid for the first time in 2014. The toxicity profile of AKB48 is unclear due to little information that mainly obtained from clinical and forensic cases; however, it is b...

Activation dynamics of the neurotensin G protein-coupled receptor 1.

A replica-exchange protocol remarkably enhances the sampling of the activation dynamics of the neurotensin receptor type 1, a G protein-coupled receptor (GPCR) and important drug target. Our work highlights the dynamic communication between conformational changes of the agonist and the G protein-binding site, via contraction-oscillation of the orthosteric pocket. It also gives insights into the mechanism by which certain mutations diminish or stimulate activation. The replica-exchange protocol effectively e...

Tolerance to WIN55,212-2 is delayed in desensitization-resistant S426A/S430A mice.

Tolerance to cannabinoid agonists can develop through desensitization of the cannabinoid receptor 1 (CB) following prolonged administration. Desensitization results from phosphorylation of CB by a G protein-coupled receptor kinase (GRK), and subsequent association of the receptor with arrestin. Mice expressing a mutant form of CB, in which the serine residues at two putative phosphorylation sites necessary for desensitization have been replaced by non-phosphorylatable alanines (S426A/S430A), display reduced...

Study of cannabinoid receptor 2 Q63R gene polymorphism in Lebanese patients with rheumatoid arthritis.

The cannabinoid (CB) receptor 2, primarily expressed in immune cells, was shown to play important immune-regulatory functions. In particular, the CB2-R63 functional variant has been shown to alter the ability of the CB2 receptor to exert its inhibitory function on T lymphocytes. The aim of this study was to investigate the association between a common dinucleotide polymorphism, Q63R, in the cannabinoid receptor 2 gene (CNR2) and rheumatoid arthritis (RA) in the Lebanese population. One hundred five unrelate...

6-Benzhydryl-4-amino-quinolin-2-ones as Potent Cannabinoid Type 1 (CB1) Receptor Inverse Agonists and Chemical Modifications for Peripheral Selectivity.

A novel series of 6-benzhydryl-4-amino-quinolin-2-ones was discovered as cannabinoid type 1 receptor (CB1R) inverse agonists based on the high-throughput screening hit, compound 1a. Structure-activity relationships were studied to improve in vitro/in vivo pharmacology and restrict distribution to the peripheral circulation. We adopted several strategies such as increasing topological polar surface area, incorporating discrete polyethylene glycol side chains and targeting P-glycoprotein (P-gp) to minimize ac...

Adenosine A-Cannabinoid CB Receptor Heteromers in the Hippocampus: Cannabidiol Blunts Δ-Tetrahydrocannabinol-Induced Cognitive Impairment.

At present, clinical interest in the plant-derived cannabinoid compound cannabidiol (CBD) is rising exponentially, since it displays multiple therapeutic properties. In addition, CBD can counteract the undesirable effects of the psychoactive cannabinoid Δ-tetrahydrocannabinol (Δ-THC) that hinder clinical development of cannabis-based therapies. Despite this attention, the mechanisms of CBD action and its interaction with Δ-THC are still not completely elucidated. Here, by combining in vivo and complement...


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