Potential mechanisms of atypical antipsychotic-induced metabolic derangement: Clues for understanding obesity and novel drug design

Coccurello, Roberto; Moles, Anna

doi:10.1016/j.pharmthera.2010.04.008

Cited by 124 publications

(100 citation statements)

References 455 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It was confirmed that Intracerebroventricular (ICV) injection of the H 1 R agonist, 2-(3-trifluoromethylphenyl)histamine (FMPH) inhibited food intake [56]. [57,58,14,59]. In particular, H 1 R blockade is recognised as a predominant target for SGA-induced weight gain compared with other receptors [4,60,61].…”

Section: H 1 R H 3 R and Sga-induced Weight Gainmentioning

confidence: 96%

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

Lian

Huang

Pai

et al. 2016

Pharmacological Research

View full text Add to dashboard Cite

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 as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 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-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve 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-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapineinduced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) 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 D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 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.

show abstract

Section: H 1 R H 3 R and Sga-induced Weight Gainmentioning

confidence: 96%

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

Lian

Huang

Pai

et al. 2016

Pharmacological Research

View full text Add to dashboard Cite

show abstract

“…Clozapine and olanzapine medications [22,23] in particular significantly influence the regulation of plasmatic insulin and leptin, although the mechanism of action remains elusive. A large number of studies have also reported a relevant role for the affinities of atypical antipsychotics for the 5HT 2A , 5HT 6 , 5HT 7 , α 1A , and particularly H 1 and 5HT 2C receptors in their obesogenic effects [24-27]. …”

Section: Introductionmentioning

confidence: 99%

“…D 2 receptor antagonism, for instance, can influence feeding behaviour [33], with an increase in 5HT 2C -mediated effects on food intake. In addition, a disruption of rewarding mechanisms by D 2 receptor blockade in the dopamine reward system might results in a disinhibition of food intake; however, these effects are of less concern for the atypical antipsychotic drugs as their 5HT 2A antagonism proprieties attenuate the disruption of reward mechanisms by D 2 antagonism [27,34]. …”

Section: Introductionmentioning

confidence: 99%

Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

et al. 2012

View full text Add to dashboard Cite

BackgroundOlanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios.ResultsWe have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors.ConclusionsWe suggest that thienobenzodiazepines 8b and 8c with lower binding affinity for the H1 receptors, but similar 5HT2A/D2 receptor binding affinity ratios to those of olanzapine. These compounds may offer a better pharmacological profile than olanzapine for treating patients with schizophrenia.

show abstract

“…The CPG for PTSD recommends nonbenzodiazepine hypnotics (e.g., zolpidem, eszopiclone, ramelteon) instead of benzodiazepines, and atypical antipsychotics are discouraged unless agitation is a severe problem. The atypical antipsychotics carry a significant risk for weight gain and related metabolic problems [138], and their use has been linked to an increased risk for obstructive sleep apnea [139].…”

Section: Managing Medical Complications Of Tbi In the Veteran With Ptsdmentioning

confidence: 99%

Review: Managing posttraumatic stress disorder in combat veterans with comorbid traumatic brain injury

Capehart¹,

Bass²

2012

JRRD

View full text Add to dashboard Cite

show abstract

Potential mechanisms of atypical antipsychotic-induced metabolic derangement: Clues for understanding obesity and novel drug design

Cited by 124 publications

References 455 publications

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

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

Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

Review: Managing posttraumatic stress disorder in combat veterans with comorbid traumatic brain injury

Contact Info

Product

Resources

About