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Review
.2019;19(16):1418-1435.
doi: 10.2174/1568026619666190708164841.

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

Affiliations
Review

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

Thuy Nguyen et al. Curr Top Med Chem.2019.

Abstract

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.

Keywords: Allosteric modulators; CB1 receptor; Neutral antagonists; Peripherally restricted antagonists; Psychiatric side effects; Therapeutics development..

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors confirm that this article has no conflict of interest.

Figures

Fig. (1).
Fig. (1).
CB1R antagonists/inverse agonists that were advanced to clinical trials.
Fig. (2).
Fig. (2).
Structures of pyrazole-based CB1R neutral antagonists.
Fig. (3).
Fig. (3).
Structures of non-pyrazole-based CB1R neutral antagonists.
Fig. (4).
Fig. (4).
Structures of pyrazole-based peripherally restricted CB1R antagonists.
Fig. (5).
Fig. (5).
Structures of non-pyrazole-based peripherally restricted CB1R antagonists.
Fig. (6).
Fig. (6).
Structures of purine-based peripherally restricted CB1R inverse agonists developed by the Maitra group.
Fig. (7).
Fig. (7).
Structures of reported CB1R NAMs.
Fig. (8).
Fig. (8).
Structures of diarylurea-based CB1R PAM-Antagonists.
See this image and copyright information in PMC

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