Ameliorating antipsychotic-induced weight gain by betahistine: mechanisms and clinical implications

摘要: Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified one of main contributors side-effects. The effects mechanisms betahistine (a H1R agonist H3 antagonist) have investigated for ameliorating SGA-induced in both animal models clinical trials. It demonstrated that co-treatment with is effective reducing gain, associated olanzapine drug-naive patients schizophrenia, well rats chronic, repeated exposure olanzapine. Betahistine can reduce food intake increase effect thermogenesis brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, ameliorate olanzapine-induced dyslipidaemia through modulation AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding 1; PPARα: Peroxisome proliferator-activated receptor-α) liver. Although reduced locomotor activity was observed from treatment rats, did not affect activity. Importantly, influence antipsychotics on serotonergic receptors key brain regions therapeutic efficacy. However, reverses upregulated dopamine D2 caused chronic administration, which may be beneficial supersensitivity often treatment. Therefore, these results provide solid evidence supporting further trials treating antipsychotics-induced gain using schizophrenia mental disorders.