ArticleMethods in enzymology2017
Metabolic Profiling of CB1 Neutral Antagonists.
Article in Methods in enzymology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Involvement of CB1R and CB2R Ligands in Sleep Disorders and Addictive Behaviors in the Last 25 Years.Pharmaceuticals (Basel, Switzerland) · 2025Review
- AM6527, a neutral CB1 receptor antagonist, suppresses opioid taking and seeking, as well as cocaine seeking in rodents without aversive effects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Novel Peripherally Selective Cannabinoid Receptor 1 Neutral Antagonist Improves Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice.ACS pharmacology & translational science · 2024Article
- Review
- Therapeutic potential of PIMSR, a novel CB1 receptor neutral antagonist, for cocaine use disorder: evidence from preclinical research.Translational psychiatry · 2022Article
- Obesity as a Condition Determined by Food Addiction: Should Brain Endocannabinoid System Alterations Be the Cause and Its Modulation the Solution?Pharmaceuticals (Basel, Switzerland) · 2021Review
- Peripherally Selective CB1 Receptor Antagonist Improves Symptoms of Metabolic Syndrome in Mice.ACS pharmacology & translational science · 2021Article
- Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs.Biomolecules · 2020Review
- A Guide to Targeting the Endocannabinoid System in Drug Design.International journal of molecular sciences · 2020Review
- Review
- Review
- Cannabinoid CBActa pharmacologica Sinica · 2019Article
- Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development.Current topics in medicinal chemistry · 2019Review
- Countering the Modern Metabolic Disease Rampage With Ancestral Endocannabinoid System Alignment.Frontiers in endocrinology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
PIMSR is among the first neutral antagonists for the CB1R and was demonstrated pharmacologically to bind to the CB1R, yet not alter calcium flux. It was further shown computationally to be able to stabilize both the active and inactive states of CB1R revealing the molecular interactions that mechanistically afford the property of neutral antagonism. PIMSR shows dramatic positive effects in reducing weight, food intake, and adiposity as well as in improving glycemic control and lipid homeostasis in high-fat diet-induced obese mice, but also shows increased ALT and liver weight as markers of liver injury with chronic administration. Further, in a separate study, 3-day administration of PIMSR in C57BL/6J mice, hepatic steatosis from an acute administration of high of ethanol was significantly reduced. Also, it partially prevented alcohol-induced increases in ALT, AST, and LDH. The differences in ALT levels in obese and nonobese mice under different test paradigms are unlikely to be due to neutral antagonism itself since other neutral antagonists (AM6545) do not exhibit liver injury. The brain levels of low micromolar would support significant brain CB1 receptor occupancy (re: Ki=17nM), thus potentially including both CNS and peripheral influences on the observed weight loss. Overall, these studies suggest that marked improvements in aspects of metabolic disease and alcoholic steatosis can be realized with CB1R neutral antagonists and hence warrants the exploration of further members of this class of cannabinoid ligands.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.