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1.
Nat Med ; 8(8): 825-30, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12118247

RESUMEN

Melanin concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight. Here we show that SNAP-7941, a selective, high-affinity MCH1 receptor (MCH1-R) antagonist, inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight. In addition, after mapping the binding sites for [(3)H]SNAP-7941 in rat brain, we evaluated its effects in a series of behavioral models. SNAP-7941 produced effects similar to clinically used antidepressants and anxiolytics in three animal models of depression/anxiety: the rat forced-swim test, rat social interaction and guinea pig maternal-separation vocalization tests. Given these observations, an MCH1-R antagonist may be useful not only in the management of obesity but also as a treatment for depression and/or anxiety.


Asunto(s)
Ansiolíticos/farmacología , Antidepresivos/farmacología , Depresores del Apetito/farmacología , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Piperidinas/farmacología , Pirimidinas/farmacología , Receptores de la Hormona Hipofisaria/antagonistas & inhibidores , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/citología , Encéfalo/metabolismo , Línea Celular , Dieta , Femenino , Cobayas , Humanos , Hormonas Hipotalámicas/química , Hormonas Hipotalámicas/metabolismo , Masculino , Melaninas/química , Melaninas/metabolismo , Estructura Molecular , Hormonas Hipofisarias/química , Hormonas Hipofisarias/metabolismo , Distribución Aleatoria , Ratas , Ratas Long-Evans , Ratas Sprague-Dawley , Ratas Wistar , Receptores de la Hormona Hipofisaria/metabolismo
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