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J Clin Invest ; 127(9): 3402-3406, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28805659

RESUMO

Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.


Assuntos
Antipsicóticos/farmacologia , Benzodiazepinas/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Antagonistas da Serotonina/farmacologia , Aumento de Peso/efeitos dos fármacos , Animais , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Composição Corporal , Peso Corporal , Feminino , Glucose/química , Teste de Tolerância a Glucose , Hiperfagia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Olanzapina , Receptor 5-HT2C de Serotonina/química
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