- |||||||||| AM6545 / Amakos Biotherap
Journal: Cannabinoids Block Fat-induced Incretin Release via CB1-dependent and CB1-independent Pathways in Intestinal Epithelium. (Pubmed Central) - Sep 25, 2024
We treated mice with conditional deletion of CB1Rs in the intestinal epithelium (IntCB1-/-) or controls (IntCB1+/+) with oil gavage to stimulate incretin release in the presence of the cannabinoid receptor agonists, WIN55,212-2 or ?9 tetrahydrocannabinol (THC), and the peripherally-restricted CB1R antagonist AM6545...In contrast, THC inhibited the secretion of incretins irrespective of CB1R expression in intestinal epithelial cells. These results indicate that cannabinoid receptor agonists can differentially inhibit incretin release via mechanisms that include intestinal epithelial CB1R-dependent and CB1R-independent mechanisms.
- |||||||||| AM6545 / Amakos Biotherap
Journal: The molecular signature of the peripheral cannabinoid receptor 1 antagonist AM6545 in adipose, liver and muscle tissue. (Pubmed Central) - Sep 10, 2024
These data indicate that acute CB1 antagonism is effective to induce phosphorylation events of signaling cascades and metabolic markers in metabolic tissues of healthy, lean mice within a 90-min time window. The observed adaptations to AM6545 treatment do not fully align with earlier in vitro and in vivo findings, which could be ascribed to differences in cell type, exposure intensity (dose and time), health status and species.
- |||||||||| betahistine intranasal (AM-201) / Altamira Therap
Preclinical, Journal: Effects of cannabinoid agonists and antagonists in male rats discriminating the synthetic cannabinoid AM2201. (Pubmed Central) - Dec 11, 2023
Next, the generalization profiles of AM411 and AM4089 with CB full agonists (JWH-018, CP-55,940, AM8936), partial agonist (?-THC), and non-cannabinoids (fentanyl, atropine) were compared...All CB drugs were more potent than ?-THC and correlation analysis confirmed that the relative behavioral potencies of CBs corresponded strongly with their relative affinities at the CB but not CB receptors. Together, our results further demonstrate that AM411 and AM4089 exhibit better pharmacological profiles compared to ?-THC, in that they are more potent and display in vivo partial agonist-like actions that are centrally mediated via CB receptors.
- |||||||||| AM4113 / MAKScientific, AM6545 - MAKScientific, Tetra Bio / Pharma
Preclinical, Journal: Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats. (Pubmed Central) - May 22, 2023
MetS rats treated with either AM6545 or AM4113 showed reduced concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the prostate compared with the MetS group. In conclusion, the CB1 antagonists AM6545 and AM4113 protect against MetS-induced BPH through their anti-proliferative, antioxidant, and anti-inflammatory effects.
- |||||||||| AM6545 - MAKScientific, Tetra Bio / Pharma
Journal: Role of CB receptors in the acute regulation of small intestinal permeability: Effects of high-fat diet. (Pubmed Central) - Aug 22, 2022
Neither the CB/CB agonist CP55,940 nor the CB neutral antagonist AM6545 altered the flux of 4kDa FITC dextran (FD4) across the jejunum or ileum of chow-fed mice...Neither ligand altered the expression of ZO-1. Our data suggest that CB receptor on the intestinal epithelium regulates tight junction protein expression and restores barrier function when it is increased following exposure to a HFD for 2 weeks.
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Journal: Cannabinoid Receptor Subtype-1 Regulates Allergic Airway Eosinophilia During Lung Helminth Infection. (Pubmed Central) - Dec 2, 2021
Roles for the eCB system in Th2 immune responses are not well understood; however, increases in its activity in response to infection suggest an immunomodulatory role. Moreover, these findings suggest a role for eCB signaling at CBRs but not cannabinoid receptor subtypes-2 in the resolution of Th2 inflammatory responses, which become host destructive over time.
- |||||||||| Acomplia (rimonabant) / Sanofi, AM6545 - MAKScientific, Tetra Bio / Pharma
Journal: Involvement of cannabinoid type 1 receptor in fasting-induced analgesia. (Pubmed Central) - Jul 29, 2021
Finally, when we performed subdiaphragmatic vagotomy to block the hunger signal from the gastrointestinal (GI) system, AM 6545 did not affect fasting-induced analgesia, but SR 141716 still reversed fasting-induced analgesia. Taken together, our results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1Rs in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasting-induced analgesic effects.
- |||||||||| CRA13 / Novartis, AM6545 - MAKScientific, Tetra Bio / Pharma
[VIRTUAL] The Role of Peripheral Cannabinoid (CB)-1 Receptors in Inflammatory Pain () - Jun 29, 2021 - Abstract #IASP2021IASP_848;
However, pain inhibition produced by systemic CB-13 administration in vivo is mediated by CB1Rs on DRG neurons, and is not affected by peripheral MOR signaling. Additionally, CB1R signaling initiated by CB-13 application produced significant HVA-ICa reductions in small DRG neurons, which potentially reduces overall nociceptive signal input to the spinal cord and represents a key ionic mechanism through which CB-13 exerts its pain inhibitory effects.
- |||||||||| Acomplia (rimonabant) / Sanofi, AM6545 - MAKScientific, Tetra Bio / Pharma
Journal: A Peripheral CB1R Antagonist Increases Lipolysis, Oxygen Consumption Rate, and Markers of Beiging in 3T3-L1 Adipocytes Similar to RIM, Suggesting that Central Effects Can Be Avoided. (Pubmed Central) - Mar 3, 2021
The brain- and peripheral-cannabinoid receptor 1 (CB1R) antagonist rimonabant (RIM) has been shown to induce weight loss and improve glucose homeostasis...Given the adverse side-effects of brain-penetrance with RIM, in this study we aimed to determine the site of action for a non-brain-penetrating CB1R antagonist AM6545...Using a lipolysis inhibitor during real-time OCR measurements, we determined that the impact of CB1R antagonism on adipocytes is driven by increased lipolysis. Thus, our data suggest the direct role of CB1R antagonism on adipocytes does not require brain penetrance, supporting the importance of focus on peripheral CB1R antagonism pharmacology for reducing the incidence of obesity and T2D.
- |||||||||| MJN110 / Scripps Research Institute, PF-04457845 / SpringWorks Therap, AM6545 - MAKScientific, Tetra Bio / Pharma
Preclinical, Journal: Endocannabinoid regulation of homeostatic feeding and stress-induced alterations in food intake in male rats. (Pubmed Central) - Jul 22, 2020
Thus, our data suggest the direct role of CB1R antagonism on adipocytes does not require brain penetrance, supporting the importance of focus on peripheral CB1R antagonism pharmacology for reducing the incidence of obesity and T2D. The current study reveals diverse roles for 2-AG and AEA in homeostatic feeding and changes in energy intake following stress.
- |||||||||| Journal: Cannabinoid Antagonist Drug Discrimination in Nonhuman Primates. (Pubmed Central) - Jul 16, 2020
Agonist substitution tests with the phytocannabinoid ∆-tetrahydrocannabinol (0.1-1.0 mg/kg), synthetic CB agonists nabilone (0.01-0.1 mg/kg), AM4054 (0.01-0.03 mg/kg), K2/Spice compound JWH-018 (0.03-0.3 mg/kg), FAAH-selective inhibitors AM3506 (0.3-5.6 mg/kg), URB597 (3.0-5.6 mg/kg), and nonselective FAAH/MGL inhibitor AM4302 (3.0-10.0 mg/kg) revealed that only agonists with CB affinity were able to reduce the rimonabant-like discriminative stimulus effects of withholding daily agonist treatment...SIGNIFICANCE STATEMENT: Despite a growing acceptance that withdrawal symptoms can emerge following the discontinuation of cannabis products, especially in high intake chronic users, there are no FDA-approved pharmacotherapies to assist those seeking treatment. The present studies systematically examined cannabinoid antagonist drug discrimination, a preclinical animal model that is designed to appraise the ability of candidate medications to attenuate the interoceptive effects that accompany abrupt cannabis abstinence.
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