Rimonabant is the first selective blocker of the cannabinoid CB1 receptors being developed for the treatment of obesity, tobacco smoking and cardiometabolic risk factors. Following 1 year of treatment, rimonabant 20 mg/day leads to greater weight loss compared with placebo. Therapy with rimonabant is also associated with favourable changes in serum lipids and an improvement in glycaemic control in Type 2 diabetics. At the same dose, rimonabant significantly increases the cigarette smoking quit rates compared with placebo. Rimonabant appears to be generally well tolerated, with primary side effects of mild nausea, diarrhoea, anxiety and depression. As an agent with a novel mechanism of action, rimonabant has the potential to be a useful adjunct to lifestyle modification in the treatment of obesity, metabolic syndrome and cigarette smoking.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1517/13543784.15.3.307 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression.
Pharmacol Res
December 2024
Department of Biomedicine, Aarhus University, Denmark; Translational Neuropsychiatry Unit, Aarhus University, Denmark. Electronic address:
Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology.
View Article and Find Full Text PDFPleasant Odor Decreases Mouse Anxiety-like Behaviors by Regulating Hippocampal Endocannabinoid Signaling.
Int J Mol Sci
October 2024
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Anxiety disorder is one of the most common neuropsychiatric disorders, and affects many people's daily activities. Although the pathogenesis and treatments of anxiety disorder have been studied for several decades, the underlying mechanisms remain elusive. Here, we provide evidence that olfactory stimuli with inhaled linalool or 2-phenylethanol decreased mouse anxiety-like behaviors and increased the activities of hippocampal dentate granule cells (DGCs).
View Article and Find Full Text PDFNew peripherally-restricted CB1 receptor antagonists, PMG-505-010 and -013 ameliorate obesity-associated NAFLD and fibrosis.
Biomed Pharmacother
November 2024
Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea. Electronic address:
Article Synopsis
- The study investigates the potential of new compounds PMG-505-010 and PMG-505-013 as peripheral CB1 receptor antagonists aimed at treating obesity and its related complications, specifically non-alcoholic fatty liver disease (NAFLD).
- These compounds were designed to limit brain exposure by modifying rimonabant, confirmed through physicochemical analysis showing reduced lipophilicity and increased polarity.
- In experiments, the new antagonists improved metabolic health in obese mice, reversing liver injury and fibrosis while avoiding CNS side effects associated with traditional CB1R antagonists.
Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome.
Mol Autism
September 2024
Center for Behavioral Sciences and Mental Health, Italian National Institute of Health, Rome, Italy.
Background: Defective mitochondria and aberrant brain mitochondrial bioenergetics are consistent features in syndromic intellectual disability disorders, such as Rett syndrome (RTT), a rare neurologic disorder that severely affects mainly females carrying mutations in the X-linked MECP2 gene. A pool of CB1 cannabinoid receptors (CB1R), the primary receptor subtype of the endocannabinoid system in the brain, is located on brain mitochondrial membranes (mtCB1R), where it can locally regulate energy production, synaptic transmission and memory abilities through the inhibition of the intra-mitochondrial protein kinase A (mtPKA). In the present study, we asked whether an overactive mtCB1R-mtPKA signaling might underlie the brain mitochondrial alterations in RTT and whether its modulation by systemic administration of the CB1R inverse agonist rimonabant might improve bioenergetics and cognitive defects in mice modeling RTT.
View Article and Find Full Text PDFNovel Peripherally Selective Cannabinoid Receptor 1 Neutral Antagonist Improves Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice.
ACS Pharmacol Transl Sci
September 2024
Center for Drug Discovery, RTI International, Research Triangle Park, North Carolina 27709-2194, United States.
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally. MASLD is characterized by clinically significant liver steatosis, and a subset of patients progress to more severe metabolic-disorder-associated steatohepatitis (MASH) with liver inflammation and fibrosis. Cannabinoid receptor 1 (CB1) antagonism is a proven therapeutic strategy for the treatment of the phenotypes that underlie MASLD, though work on early centrally penetrant compounds largely ceased following adverse psychiatric indications in humans.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!