Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications
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作者:
Lian, Jiamei
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Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Univ Wollongong, Sch Med, Wollongong, NSW 2522, AustraliaIllawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Lian, Jiamei
[1
,2
]
Huang, Xu-Feng
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Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Univ Wollongong, Sch Med, Wollongong, NSW 2522, AustraliaIllawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Huang, Xu-Feng
[1
,2
]
Pai, Nagesh
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Univ Wollongong, Sch Med, Wollongong, NSW 2522, AustraliaIllawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Pai, Nagesh
[2
]
Deng, Chao
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Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Univ Wollongong, Sch Med, Wollongong, NSW 2522, AustraliaIllawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
Deng, Chao
[1
,2
]
机构:
[1] Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia
[2] Univ Wollongong, Sch Med, Wollongong, NSW 2522, Australia
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 H-1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H-3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naive patients with schizophrenia, as well as in the animal models of both drug-naive rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPK alpha (NPY: neuropeptide Y; AMPK alpha: AMP-activated protein kinase alpha) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPK alpha-SREBP-1-PPAR alpha-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPAR alpha: Peroxisome proliferator-activated receptor-alpha) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D-2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D-2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental disorders. (C) 2016 Elsevier Ltd. All rights reserved.
机构:
Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Attux, Cecilia
Martini, Larissa C.
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Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Martini, Larissa C.
de Araujo, Celia Maria
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Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
de Araujo, Celia Maria
Roma, Ana Maria
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Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Roma, Ana Maria
Reis, Andre F.
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Univ Fed Sao Paulo, Dept Endocrinol, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Reis, Andre F.
Bressan, Rodrigo A.
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Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
机构:
Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Attux, Cecilia
Martini, Larissa C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Martini, Larissa C.
de Araujo, Celia Maria
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h-index: 0
机构:
Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
de Araujo, Celia Maria
Roma, Ana Maria
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机构:
Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Roma, Ana Maria
Reis, Andre F.
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h-index: 0
机构:
Univ Fed Sao Paulo, Dept Endocrinol, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil
Reis, Andre F.
Bressan, Rodrigo A.
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机构:
Univ Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, BrazilUniv Fed Sao Paulo, Schizophrenia Program PROESQ, Dept Psychiat, Sao Paulo, Brazil