scholarly journals New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists

2021 ◽  
Vol 22 (20) ◽  
pp. 11212
Author(s):  
Manuel Faúndez-Parraguez ◽  
Carlos Alarcón-Miranda ◽  
Young Hwa Cho ◽  
Hernán Pessoa-Mahana ◽  
Carlos Gallardo-Garrido ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Docking Studies ◽  
Receptor Type ◽  
Intracellular Camp ◽  
Type I ◽  
Type Ii ◽  
New Information ◽  
Starting Point ◽  
Inflammatory Processes

The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.

Synthesis, Pharmacological Evaluation, and Docking Studies of Novel Pyridazinone-Based Cannabinoid Receptor Type 2 Ligands

ChemMedChem ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. 1102-1114
Author(s):  
Giulio Ragusa ◽  
Serena Bencivenni ◽  
Paula Morales ◽  
Tyra Callaway ◽  
Dow P. Hurst ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Docking Studies ◽  
Receptor Type ◽  
Pharmacological Evaluation ◽  
Cannabinoid Receptor Type 2

scholarly journals Cannabinoid receptor type 2 gene is associated with human osteoporosis

2005 ◽  
Vol 14 (22) ◽  
pp. 3389-3396 ◽  
Author(s):  
Meliha Karsak ◽  
Martine Cohen-Solal ◽  
Jan Freudenberg ◽  
Agnes Ostertag ◽  
Caroline Morieux ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 2

scholarly journals Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Andrea Mastinu ◽  
Marika Premoli ◽  
Giulia Ferrari-Toninelli ◽  
Simone Tambaro ◽  
Giuseppina Maccarinelli ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
History Of ◽  
Health And Disease ◽  
Pharmacological Potential ◽  
The Brain ◽  
Synthesis And Degradation

Abstract The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response. In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made. Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.

scholarly journals Cannabinoid Receptor Type 2 (CB2) Dependent and Independent Effects of WIN55,212-2 on Atherosclerosis in Ldlr-null Mice

2015 ◽  
Vol 3 (2) ◽  
pp. 53-63 ◽  
Author(s):  
Douglas Thewke ◽  
◽  
Courtney Netherland-Van Dyke ◽  
Ward Rodgers ◽  
Makenzie Fulmer ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 2 ◽  
Independent Effects

scholarly journals Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

2020 ◽  
Vol 21 (11) ◽  
pp. 3809 ◽  
Author(s):  
Francesca Rossi ◽  
Chiara Tortora ◽  
Maura Argenziano ◽  
Alessandra Di Paola ◽  
Francesca Punzo
Keyword(s):  
Cannabinoid Receptor ◽  
Protective Role ◽  
Receptor Type ◽  
Macrophage Phenotype ◽  
Small Vessels ◽  
Global Pandemic ◽  
Cannabinoid Receptor Type 2 ◽  
Novel Coronavirus

In late December 2019, a novel coronavirus (SARS-CoV-2 or CoV-19) appeared in Wuhan, China, causing a global pandemic. SARS-CoV-2 causes mild to severe respiratory tract inflammation, often developing into lung fibrosis with thrombosis in pulmonary small vessels and causing even death. COronaVIrus Disease (COVID-19) patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells. Men show higher susceptibility to SARS-CoV-2 infection than women, likely due to estrogens production. The protective role of estrogens, as well as an immune-suppressive activity that limits the excessive inflammation, can be mediated by cannabinoid receptor type 2 (CB2). The role of this receptor in modulating inflammation and immune response is well documented in fact in several settings. The stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells. For these reasons, we hypothesize that CB2 receptor can be a therapeutic target in COVID-19 pandemic emergency.

Interleukin-1 alpha stimulates dopamine release by activating type II protein kinase A in PC-12 cells

1995 ◽  
Vol 269 (6) ◽  
pp. E1083-E1088
Author(s):  
A. Joseph ◽  
A. Kumar ◽  
N. A. O'Connell ◽  
R. K. Agarwal ◽  
A. R. Gwosdow
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Dopamine Release ◽  
Interleukin 1 ◽  
Intracellular Camp ◽  
Type I ◽  
Camp Accumulation ◽  
Type Ii ◽  
Pc 12 Cells ◽  
Kinase A

A recent study from this laboratory [A. R. Gwosdow, N. A. O'Connell, and A. B. Abou-Samra. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E461-E466, 1992] showed that the inflammatory mediator interleukin-1 alpha (IL-1 alpha) stimulates catecholamine release from primary cultures of rat adrenal cells. The present studies were conducted to determine whether 1) IL-1 alpha stimulates catecholamine/dopamine release from the adrenal medullary cell line PC-12 and 2) the adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) pathway is involved in IL-1 alpha-induced dopamine release from PC-12 cells. The results indicate that IL-1 alpha significantly (P < 0.05) elevated dopamine release after a 24-h incubation period. IL-1 alpha did not stimulate cAMP accumulation at any time period between 5 min and 2 h. In contrast, forskolin-treated cells elevated (P < 0.05) intracellular cAMP levels and increased dopamine release. Because IL-1 alpha did not affect cAMP accumulation, the effect of IL-1 alpha on PKA activity was investigated. IL-1 alpha increased (P < 0.05) PKA activity at 15 and 30 min and returned to control levels by 1 h. Forskolin also increased (P < 0.05) PKA activity. The type of PKA activated (P < 0.05) by IL-1 alpha was type II PKA. In contrast, forskolin activated (P < 0.05) type I and type II PKA. Inhibition of PKA with the PKA inhibitor H-8 blocked PKA activity and dopamine secretion by both IL-1 alpha and forskolin in PC-12 cells. These observations demonstrate that 1) IL-1 alpha stimulated dopamine release from PC-12 cells by activating PKA, 2) the mechanism of IL-1 alpha activation of PKA does not involve detectable increases in intracellular cAMP accumulation, and 3) IL-1 alpha activates type II PKA, which is used by IL-1 alpha to stimulate dopamine secretion from PC-12 cells.

scholarly journals Inverse Agonism of Cannabinoid Receptor Type 2 Confers Anti-inflammatory and Neuroprotective Effects Following Status Epileptics

2020 ◽  
Vol 57 (6) ◽  
pp. 2830-2845 ◽  
Author(s):  
Ying Yu ◽  
Lexiao Li ◽  
Davis T. Nguyen ◽  
Suni M. Mustafa ◽  
Bob M. Moore ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Neuroprotective Effects ◽  
Inverse Agonism ◽  
Cannabinoid Receptor Type 2 ◽  
Anti Inflammatory
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