Dataset Information

Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro.

ABSTRACT: Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting ?(7)-reductase, ?(8,7)-isomerase, and ?(14)-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had the same targets as haloperidol at inhibiting cholesterol biosynthesis, although with different relative activities (ziprasidone > haloperidol > risperidone). In contrast, clozapine mainly affected ?(24)-reductase and ?(8,7)-isomerase activities. These amphiphilic drugs also interfered with the LDL-derived cholesterol egress from the endosome/lysosome compartment, thus further reducing the cholesterol content in the endoplasmic reticulum. This triggered a homeostatic response with the stimulation of sterol regulatory element-binding protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the synthesis of complex lipids (phospholipids and triacylglycerides). Once the antipsychotics were removed from the medium, a rebound in the cholesterol biosynthesis rate was detected, and the complex-lipid synthesis further increased. In this condition, apolipoprotein B secretion was also stimulated as demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be relevant in the metabolic side effects of antipsychotics, especially hypertriglyceridemia.

SUBMITTER: Canfran-Duque A

PROVIDER: S-EPMC3588861 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro.

Canfrán-Duque Alberto A Casado María E ME Pastor Oscar O Sánchez-Wandelmer Jana J de la Peña Gema G Lerma Milagros M Mariscal Paloma P Bracher Franz F Lasunción Miguel A MA Busto Rebeca R

Journal of lipid research 20121121 2

Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting Δ(7)-reductase, Δ(8,7)-isomerase, and Δ(14)-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthe ...[more]

PMID: 23175778

Similar Datasets

Project description:BackgroundIn many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics.ObjectivesTo evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.Search strategyWe searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO.Selection criteriaWe included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses.Data collection and analysisWe extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.Main resultsThe review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67).Authors' conclusionsThere is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

Dataset Information

Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro.

Publications

Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets