Rimonabant, Gastrointestinal Motility and Obesity

Sun, Yan; Chen, Jiande D.Z.

doi:10.2174/157015912803217297

Cited by 19 publications

(12 citation statements)

References 68 publications

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“…Accordingly, the CB 1 R antagonist and rimonabant was successfully used in humans to fight obesity. However, because of adverse psychiatric side effects, the drug was withdrawn from the market . This particular failure illustrates the need to develop new drugs that are effective and safe in the long‐term in order to successfully fight obesity and other metabolic disorders.…”

Section: How Do Cb1r Control Food Intake?mentioning

confidence: 99%

Dissecting the cannabinergic control of behavior: The where matters

et al. 2015

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The endocannabinoid system is the target of the main psychoactive component of the plant Cannabis sativa, the Δ(9)-tetrahydrocannabinol (THC). This system is composed by the cannabinoid receptors, the endogenous ligands, and the enzymes involved in their metabolic processes, which works both centrally and peripherally to regulate a plethora of physiological functions. This review aims at explaining how the site-specific actions of the endocannabinoid system impact on memory and feeding behavior through the cannabinoid receptors 1 (CB1 R). Centrally, CB1 R is widely distributed in many brain regions, different cell types (e.g. neuronal or glial cells) and intracellular compartments (e.g. mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB1 R according to their cell-type localization (e.g. glutamatergic or GABAergic neurons). Thus, understanding the cellular and subcellular function of CB1 R will provide new insights and aid the design of new compounds in cannabinoid-based medicine. Also watch the Video Abstract.

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Section: How Do Cb1r Control Food Intake?mentioning

confidence: 99%

Dissecting the cannabinergic control of behavior: The where matters

et al. 2015

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“…Fig. S1A) was the first selective antagonist described for CB 1 receptors in in vitro and in vivo studies [9][10][11], and it was introduced into clinical use in 2006 as an anti-obesity agent. Rimonabant use was associated with reductions in body weight and waist circumference, and improvements in the profile of metabolic risk factors in patients who were overweight or obese and had atherogenic dyslipidemia [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling

Ruz‐Maldonado

Liu

Atanes

et al. 2020

Cell. Mol. Life Sci.

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Aims Endocannabinoids are lipid mediators involved in the regulation of glucose homeostasis. They interact with the canonical cannabinoid receptors CB 1 and CB 2 , and it is now apparent that some cannabinoid receptor ligands are also agonists at GPR55. Thus, CB 1 antagonists such as SR141716A, also known as rimonabant, and AM251 act as GPR55 agonists in some cell types. The complex pharmacological properties of cannabinoids make it difficult to fully identify the relative importance of CB 1 and GPR55 in the functional effects of SR141716A, and AM251. Here, we determine whether SR141716A and AM251 regulation of mouse and human islet function is through their action as GPR55 agonists. Methods Islets isolated from Gpr55 +/+ and Gpr55 −/− mice and human donors were incubated in the absence or presence of 10 µM SR141716A or AM251, concentrations that are known to activate GPR55. Insulin secretion, cAMP, IP 1 , apoptosis and β-cell proliferation were quantified by standard techniques. Results Our results provide the first evidence that SR141716A and AM251 are not GPR55 agonists in islets, as their effects are maintained in islets isolated from Gpr55 −/− mice. Their signalling through G q-coupled cascades to induce insulin secretion and human β-cell proliferation, and protect against apoptosis in vitro, indicate that they have direct beneficial effects on islet function. Conclusion These observations may be useful in directing development of peripherally restricted novel therapeutics that are structurally related to SR141716A and AM251, and which potentiate glucose-induced insulin secretion and stimulate β-cell proliferation.

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“…Gastric emptying plays an important role in the intestinal exposure to nutrients and satiety ( 22 , 23 ), and it is closely related to glycemic control since it acts as a major determinant of postprandial glycemic regulation ( 24 ). In our study, both the F1 and F2 generations had changes in gastric motility and, in parallel, their glycemic levels were higher compared to the CONT and F3 groups.…”

Section: Discussionmentioning

confidence: 99%

“…Small bowel transit regulates nutrient absorption and seems to be related to the development of obesity ( 23 ). In our study, the F2 generation had a delayed MCAT and MSITT compared to all groups, which reinforced that some programmed effects can be transmitted to subsequent generations ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring

Machado

Gama

Beckmann

et al. 2021

Braz J Med Biol Res

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The interplay between obesity and gastrointestinal (GI) motility is contradictory, and the transgenerational influence on this parameter is unknown. We aimed to evaluate the GI function in a model of paternal obesity and two subsequent generations of their male offspring. Newborn male rats were treated with monosodium glutamate (MSG) and composed the F1 generation, while control rats (CONT) received saline. At 90 days, male F1 were mated with non-obese females to obtain male offspring (F2), which later mated with non-obese females for obtaining male offspring of F3 generation. Lee Index analysis was adopted to set up the obesity groups. Alternating current biosusceptometry (ACB) technique was employed to calculate GI transit parameters: mean gastric emptying time (MGET), mean cecum arrival time (MCAT), mean small intestinal transit time (MSITT), and gastric frequency and amplitude of contractions. Glucose, insulin, and leptin levels and duodenal morphometry were measured. F1 obese rats showed a decrease in the frequency and amplitude of gastric contractions, while obese rats from the F2 generation showed accelerated MGET and delayed MCAT and MSITT. Glucose and leptin levels were increased in F1 and F2 generations. Insulin levels decreased in F1, F2, and F3 generations. Duodenal morphometry was altered in all three generations. Obesity may have paternal transgenerational transmission, and it provoked disturbances in the gastrointestinal function of three generations.

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Rimonabant, Gastrointestinal Motility and Obesity

Cited by 19 publications

References 68 publications

Dissecting the cannabinergic control of behavior: The where matters

Dissecting the cannabinergic control of behavior: The where matters

The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling

Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring

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