Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors.
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.
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.
Although pharmacological blockade of CB1R has been effective for the treatment of obesity and tobacco addiction, precise distribution of CB1R within the brain and potential changes by obesity or nicotine exposure have not been thoroughly addressed.
Antagonists of peripheral type 1 cannabinoid receptors (CB1) may have utility in the treatment of obesity, liver disease, metabolic syndrome and dyslipidemias.
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.
Cannabinoid 1 (CB1) receptor antagonists exhibit pharmacological properties favorable for the treatment of obesity and other related metabolic disorders.
Consideration of both biological and cultural evolution justifies the design of improved pharmacological treatments for obesity and Type 2 diabetes (T2D) that focus on peripheral CB1R antagonism.
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.
Endocannabinoid is identified as the emerging target for the treatment of obesity as Cannabinoid 1 (CB1) receptor over-activation resulted in abdominal obesity.
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.
In obese Zucker rats, a significant decrease in CB1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment.
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.
In order to assess the impact of CNR1 variability on the development of dyslipidemia in the community, we genotyped this locus in all subjects with class III obesity (body mass index >40 kg/m(2)) participating in a population-based biobank of similar ancestry.
In pharmacological evaluation, the synthesized compounds (23, 25, 27 and 34) showed significant decrease in food intake suggesting their potential application in the management of obesity through CB1 receptor antagonist activity.
In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice.