scholarly journals The psychiatric side-effects of rimonabant

2009 ◽  
Vol 31 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Fabrício A. Moreira ◽  
José Alexandre S. Crippa
Keyword(s):  
Smoking Cessation ◽  
Side Effects ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Receptor Antagonists ◽  
Literature Searches ◽  
Antidepressant Effects ◽  
Psychiatric Side Effects ◽  
New Compounds ◽  
Cb1 Receptor Antagonists

OBJECTIVE: Experimental evidence has suggested that drugs that enhance cannabinoid type-1 (CB1) receptor activity may induce anxiolytic and antidepressant effects, whilst the opposite has been reported with antagonists. Thus, the objective of the present review is to discuss the potential psychiatric side-effects of CB1 receptor antagonists, such as rimonabant, which has been recently marketed in several countries for the treatment of smoking cessation, obesity and associated metabolic disorders. METHOD: Literature searches were performed in PubMed and SciELO databases up to February 2009. The terms searched were "obesity", "rimonabant", "cannabinoids", "unwanted effects", "diabetes", "smoking cessation" and "side-effects". RESULTS: Clinical trials have revealed that rimonabant may promote weight loss in obese patients, although it may also induce symptoms of anxiety and depression. DISCUSSION: Patients taking CB1 receptor antagonists should be carefully investigated for psychiatric side-effects. These drugs should not be prescribed for those already suffering from mental disorders. Nevertheless, the development of new compounds targeting the endocannabinoid system for the treatment of several conditions would be necessary and opportune.

scholarly journals Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development

2019 ◽  
Vol 19 (16) ◽  
pp. 1418-1435 ◽  
Author(s):  
Thuy Nguyen ◽  
Brian F. Thomas ◽  
Yanan Zhang
Keyword(s):  
Side Effects ◽  
Large Body ◽  
Cb1 Receptor ◽  
Allosteric Modulators ◽  
Cannabinoid Cb1 Receptor ◽  
Physiological Pathways ◽  
Treatment Of Obesity ◽  
Psychiatric Side Effects ◽  
Anxiety Depression ◽  
Cb1 Receptor Antagonists

The Cannabinoid CB1 Receptor (CB1R) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. 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. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the CB1R in the last two decades.

Cannabinoid Cb1 Receptor Antagonists/Inverse Agonists and Food-Seeking Behavior

2011 ◽  
pp. 441-456
Author(s):  
John D. Salamone ◽  
Kelly Sink ◽  
Kristen N. Segovia ◽  
Patrick A. Randall ◽  
Peter J. McLaughlin ◽  
...  
Keyword(s):  
Cb1 Receptor ◽  
Cannabinoid Cb1 Receptor ◽  
Receptor Antagonists ◽  
Inverse Agonists ◽  
Seeking Behavior ◽  
Food Seeking ◽  
Cb1 Receptor Antagonists

Celecoxib, ibuprofen, and indomethacin alleviate depression-like behavior induced by interferon-alfa in mice

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Azadeh Mesripour ◽  
Shahrzad Shahnooshi ◽  
Valiollah Hajhashemi
Keyword(s):  
Side Effects ◽  
Forced Swimming Test ◽  
Interferon Alfa ◽  
Interferon Α ◽  
High Dose ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Inflammatory Drugs ◽  
Swimming Test ◽  
Psychiatric Side Effects

AbstractBackgroundInterferon-α (IFNα) therapy causes psychiatric side effects, including depression that may result in poor compliance of therapy. It is important to find alternative therapies for the prevention of IFNα induced depression. Non-steroidal anti-inflammatory drugs (NSAIDs) have been useful in depressive disorder. Therefore the effects of celecoxib, ibuprofen, and indomethacin were evaluated following IFNα-induced depression in mice.MethodsMale albino mice weighing 26 ± 2 g were used. Depression was induced by IFNα (16 × 105 IU/kg, SC) for six consecutive days. Animals were first subject to the locomotor test, then the splash test and finally the forced swimming test (FST) on the 7th day. The NSAIDs were administered (IP) either one single dose before the test, or simultaneously with IFNα.Resultslocomotor activity was only impaired by ibuprofen high dose (75 mg/kg), thus it was not further evaluated. Following IFNα therapy depression-like behaviors were observed; significant changes during the splash test (grooming time 24 ± 7 sec vs. control 63 ± 7 sec), the FST (immobility time 166  ± 15 sec vs. control 128  ± 6 sec), and sucrose preference reduced to 64 ± 0.8%. The NSAIDs noticeably reduced the immobility time in FST, while grooming time was increased. Celecoxib and indomethacin single doses were effective while ibuprofen showed better antidepressant effects when it was administered along with IFNα.ConclusionsThe NSAIDs were able to prevent IFNα induced depression in mice. NSAIDs administration with IFNα does not interfere with clinical benefit effects of IFNα and they could also be useful to prevent IFNα psychiatric side effects, thus further clinical trials are suggested.

scholarly journals Cannabinoids for clinicians: the rise and fall of the cannabinoid antagonists

2009 ◽  
Vol 161 (5) ◽  
pp. 655-662 ◽  
Author(s):  
Helen Butler ◽  
Márta Korbonits
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Side Effects ◽  
Endocannabinoid System ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
Concise Review ◽  
Psychiatric Side Effects ◽  
Lipid Parameters ◽  
Cannabinoid Antagonists

The endocannabinoid system has emerged as a significant player in the control of energy balance and metabolism, through its direct central and peripheral effects, as well as via its interaction with other appetite-regulating pathways. There is mounting evidence that the endocannabinoid system is overactive in obesity and were it possible to safely dampen-down the elevated endocannabinoid tone, lipid and carbohydrate profiles could be improved and weight loss induced. The series of randomised clinical trials showed reproducible beneficial effects on weight, HbA1c and lipid parameters, in addition to other cardiovascular risk factors. However, to date, clinical developments have been halted because of psychiatric side effects. Although recent evidence has highlighted the importance of an appetite-independent, peripheral mode of action, it is still unclear whether selectively blocking the peripheral system could potentially solve the problem of the central side effects, which thus far has led to the demise of the cannabinoid antagonists as useful pharmaceuticals. In this concise review, we summarise the data on the metabolic effects of the cannabinoid pathway and its antagonists.

Identifying the structural features and diversifying the chemical domain of peripherally acting CB1 receptor antagonists using molecular modeling techniques

RSC Advances ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 1466-1483 ◽  
Author(s):  
Mayank Kumar Sharma ◽  
Prashant R. Murumkar ◽  
Guanglin Kuang ◽  
Yun Tang ◽  
Mange Ram Yadav
Keyword(s):  
Molecular Modeling ◽  
Virtual Screening ◽  
3D Qsar ◽  
Structural Features ◽  
Cb1 Receptor ◽  
Receptor Antagonists ◽  
Modeling Techniques ◽  
Qsar Models ◽  
Cb1 Receptor Antagonists

A four featured pharmacophore and predictive 3D-QSAR models were developed which were used for virtual screening of the Asinex database to get chemically diverse hits of peripherally active CB1 receptor antagonists.

Advances in patented CB1 receptor antagonists for obesity

2018 ◽  
Vol 7 (5) ◽  
pp. 169-173 ◽  
Author(s):  
Mange Ram Yadav ◽  
Prashant R Murumkar
Keyword(s):  
Cb1 Receptor ◽  
Receptor Antagonists ◽  
Cb1 Receptor Antagonists
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