The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake
(2008) Cell Metabolism — Vol. 7, n° 1, p. 68-78 (2008)
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- Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy. However, the physiological mechanisms by which these agents modulate human energy balance are incompletely elucidated. Here, we describe a comprehensive clinical research study of taranabant, a structurally novel acyclic CB1 R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [F-18]MK-9470 confirmed central nervous system receptor occupancy levels (similar to 10%-40%) associated with energy balance/weight- loss effects in animals. In a 12-week weight-loss study, taranabant induced statistically significant weight loss compared to placebo in obese subjects over the entire range of evaluated doses (0.5, 2, 4, and 6 mg once per day) (p < 0.001). Taranabant treatment was associated with dose-related increased incidence of clinical adverse events, including mild to moderate gastrointestinal and psychiatric effects. Mechanism-of-action studies suggest that engagement of the CB1R by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation.
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Addy, C., Van Laere, K., De Lepeleire, I., Cilissen, C., de Hoon, J., Bormans, G. M., Depre, M., & et al. (2008). The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metabolism, 7(1), 68-78. https://doi.org/10.1016/j.cmet.2007.11.012 (Original work published 2008)