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Obesity

CB1R inverse agonists—antiobesity effects without the neuropsychiatric adverse effects?

Nature Reviews Endocrinology volume 8, page 564 (2012)Cite this article

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The endocannabinoid system is overactive in obesity and CB1R inverse agonists, such as rimonabant, showed promise for the treatment of obesity, especially as these agents also reduced associated metabolic complications. However, therapeutic development of this class of drugs was halted owing to neuropsychiatric adverse effects, including anxiety and depression.

Tam et al. synthesized a peripherally acting CB1R inverse agonist, JD5037, by altering the structure of the CB1R inverse agonist SLV319 to reduce its brain penetrance but retain its high affinity for CB1R. The researchers compared the antiobesity effects of JD5037 with those of SLV319 in mice with diet-induced obesity.

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ORIGINAL RESEARCH PAPER

  1. Tam, J. et al. Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metabolism doi:10.1016/j.cmet.2012.07.002

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  1. Carol Wilson
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Wilson, C. CB1R inverse agonists—antiobesity effects without the neuropsychiatric adverse effects?. Nat Rev Endocrinol 8, 564 (2012). https://doi.org/10.1038/nrendo.2012.145

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