Selonabant

A cannabinoid receptor antagonist

Selonabant
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CAS Number	444912-48-5
PubChem	115237
DrugBank
ChemSpider	103040
KEGG	D08995

Selonabant (also known by its developmental code name SR147778) is a cannabinoid receptor type 1 (CB1) antagonist that was under investigation for the treatment of obesity and related metabolic disorders. It was developed by Sanofi-Aventis but was never marketed.

Pharmacology

Selonabant acts as a selective antagonist of the cannabinoid receptor type 1 (CB1), which is primarily found in the central nervous system and peripheral tissues. By blocking the action of endocannabinoids at the CB1 receptor, selonabant was intended to reduce appetite and promote weight loss. The CB1 receptor is involved in the regulation of appetite, pain sensation, mood, and memory.

Development and Clinical Trials

Chemical structure of Selonabant

The development of selonabant was part of a broader effort to create drugs that could combat obesity by targeting the endocannabinoid system. Initial studies suggested that CB1 antagonists like selonabant could help reduce food intake and body weight in animal models. However, the development of selonabant was halted due to concerns about its safety profile and the emergence of adverse psychiatric effects, which were also observed with other CB1 antagonists such as rimonabant.

Mechanism of Action

The mechanism of action of selonabant involves the inhibition of the CB1 receptor, which is a G protein-coupled receptor (GPCR) that mediates the effects of endocannabinoids like anandamide and 2-arachidonoylglycerol (2-AG). By blocking these effects, selonabant was hypothesized to decrease the rewarding properties of food and reduce caloric intake.

Potential Applications

While the primary focus of selonabant's development was on obesity and metabolic syndrome, there was also interest in its potential applications for other conditions such as addiction, anxiety, and depression. The endocannabinoid system is implicated in a wide range of physiological processes, and modulation of this system could have therapeutic benefits for various disorders.

Discontinuation

The development of selonabant was discontinued due to safety concerns, particularly the risk of psychiatric side effects such as depression and anxiety. These concerns were significant enough to outweigh the potential benefits of the drug in treating obesity and related conditions.

Related pages

• Cannabinoid receptor type 1
• Endocannabinoid system
• Obesity
• Rimonabant