To analyze the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018 as the peripherally restricted cannabinoid 1 receptor (CB1R) antagonist.
Discovery of N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity.
Therapeutics aimed at blocking the cannabinoid 1 (CB1) receptor for treatment of obesity resulted in significant improvements in liver function, glucose uptake and pancreatic β-cell function independent of weight loss or CB1 receptor blockade in the brain, suggesting that peripherally-acting only CB1 receptor blockers may be useful therapeutic agents.
All classical CB1R blockers were centrally acting appetite suppressants and decreased body weight and food intake in an obesity-dependent manner, with only slight effects on metabolic syndrome markers.
Significant progress was made with the discovery of rimonabant, a selective CB1 receptor (CB1R) antagonist (also an inverse agonist), as a promising therapeutic for SUDs and obesity.
Small molecules targeting peripheral CB1 receptors have therapeutic potential in a variety of disorders including obesity-related, hormonal, and metabolic abnormalities, while avoiding the psychoactive effects in the central nervous system.
Given CB1 receptors remain as potential pharmacological targets to fight against obesity and T2D, we wanted to explore the metabolic impact of this compound in an animal model of obesity and pre-diabetes as well as the lack of relevant actions in related central processes such as anxiety.
Thus, the current study indicates that TXX-522 is a novel and potent peripherally acting selective CB1R antagonist with the potential to control obesity and related metabolic disorders.
Endocannabinoid is identified as the emerging target for the treatment of obesity as Cannabinoid 1 (CB1) receptor over-activation resulted in abdominal obesity.
The activated cannabinoid receptor 1 (CB1R) is exclusively responsible for food intake and weight gain and regulates several pathological features associated with obesity in mammals.
A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction.
In light of recent advances and complexity in the field, we review cannabinoid-based therapeutic strategies for the treatment of obesity and how peripheral restriction of CB1R antagonists may provide a different mechanism of weight loss without the central adverse effects.
Cannabinoid 1 (CB1) receptor antagonists exhibit pharmacological properties favorable for the treatment of obesity and other related metabolic disorders.
Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated.
Previous studies have shown that the CB1 receptor antagonist reverses steatohepatitis and its related features of metabolic syndrome, such as obesity and type 2 diabetes.
To explore the pharmacological utility of CB1R inhibition for the treatment of obesity, we evaluated the efficacy of N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364) and determined the relationship between efficacy and brain CB1R occupancy in rodents.
We determined whether CB1 receptor splice variants and messenger RNA (mRNA) levels in perirenal and subcutaneous adipose tissues are associated with obesity and metabolic syndrome (MetS).