The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake.
Cell Metab
; 7(1): 68-78, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-18177726
ABSTRACT
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 CB1R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [(18)F]MK-9470 confirmed central nervous system receptor occupancy levels ( approximately 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Ingestão de Energia
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Redução de Peso
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Receptor CB1 de Canabinoide
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Metabolismo Energético
/
Amidas
Tipo de estudo:
Clinical_trials
/
Health_economic_evaluation
Limite:
Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article