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An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine

Over the past two decades, there has been a notable rise in the use of antipsychotic drugs, as they are used to treat an increasing number of neuropsychiatric disorders. This rise has been led predominantly by greater use of the second generation antipsychotic (SGA) drugs, which have a low incidence...

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Autores principales: Wu, Claire, Yuen, Jessica, Boyda, Heidi N., Procyshyn, Ric M., Wang, Cathy K., Asiri, Yahya I., Pang, Catherine C. Y., Honer, William G., Barr, Alasdair M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177840/
https://www.ncbi.nlm.nih.gov/pubmed/25254366
http://dx.doi.org/10.1371/journal.pone.0107116
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author Wu, Claire
Yuen, Jessica
Boyda, Heidi N.
Procyshyn, Ric M.
Wang, Cathy K.
Asiri, Yahya I.
Pang, Catherine C. Y.
Honer, William G.
Barr, Alasdair M.
author_facet Wu, Claire
Yuen, Jessica
Boyda, Heidi N.
Procyshyn, Ric M.
Wang, Cathy K.
Asiri, Yahya I.
Pang, Catherine C. Y.
Honer, William G.
Barr, Alasdair M.
author_sort Wu, Claire
collection PubMed
description Over the past two decades, there has been a notable rise in the use of antipsychotic drugs, as they are used to treat an increasing number of neuropsychiatric disorders. This rise has been led predominantly by greater use of the second generation antipsychotic (SGA) drugs, which have a low incidence of neurological side-effects. However, many SGAs cause metabolic dysregulation, including glucose intolerance and insulin resistance, thus increasing the risk of cardiometabolic disorders. The metabolic effects of the novel SGA lurasidone, which was approved by the Food and Drug Administration in 2010, remain largely unknown. As rodent models accurately predict the metabolic effects of SGAs in humans, the aim of the present study was to use sophisticated animal models of glucose tolerance and insulin resistance to measure the metabolic effects of lurasidone. In parallel, we compared the SGA olanzapine, which has established metabolic effects. Adult female rats were treated with vehicle, lurasidone (0.2, 0.8 or 2.0 mg/kg, s.c.) or olanzapine (10.0 mg/kg, s.c.) and subjected to the glucose tolerance test (GTT). Separate groups of rats were treated with vehicle, lurasidone (0.2, 0.8 or 2.0 mg/kg, s.c.) or olanzapine (1.5 and 15 mg/kg, s.c.) and tested for insulin resistance with the hyperinsulinemic-euglycemic clamp (HIEC). Compared to vehicle treated animals, lurasidone caused mild glucose intolerance in the GTT with a single dose, but there was no effect on insulin resistance in the GTT, measured by HOMA-IR. The HIEC also confirmed no effect of lurasidone on insulin resistance. In contrast, olanzapine demonstrated dose-dependent and potent glucose intolerance, and insulin resistance in both tests. Thus, in preclinical models, lurasidone demonstrates mild metabolic liability compared to existing SGAs such as olanzapine. However, confirmation of these effects in humans with equivalent tests should be confirmed.
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spelling pubmed-41778402014-10-02 An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine Wu, Claire Yuen, Jessica Boyda, Heidi N. Procyshyn, Ric M. Wang, Cathy K. Asiri, Yahya I. Pang, Catherine C. Y. Honer, William G. Barr, Alasdair M. PLoS One Research Article Over the past two decades, there has been a notable rise in the use of antipsychotic drugs, as they are used to treat an increasing number of neuropsychiatric disorders. This rise has been led predominantly by greater use of the second generation antipsychotic (SGA) drugs, which have a low incidence of neurological side-effects. However, many SGAs cause metabolic dysregulation, including glucose intolerance and insulin resistance, thus increasing the risk of cardiometabolic disorders. The metabolic effects of the novel SGA lurasidone, which was approved by the Food and Drug Administration in 2010, remain largely unknown. As rodent models accurately predict the metabolic effects of SGAs in humans, the aim of the present study was to use sophisticated animal models of glucose tolerance and insulin resistance to measure the metabolic effects of lurasidone. In parallel, we compared the SGA olanzapine, which has established metabolic effects. Adult female rats were treated with vehicle, lurasidone (0.2, 0.8 or 2.0 mg/kg, s.c.) or olanzapine (10.0 mg/kg, s.c.) and subjected to the glucose tolerance test (GTT). Separate groups of rats were treated with vehicle, lurasidone (0.2, 0.8 or 2.0 mg/kg, s.c.) or olanzapine (1.5 and 15 mg/kg, s.c.) and tested for insulin resistance with the hyperinsulinemic-euglycemic clamp (HIEC). Compared to vehicle treated animals, lurasidone caused mild glucose intolerance in the GTT with a single dose, but there was no effect on insulin resistance in the GTT, measured by HOMA-IR. The HIEC also confirmed no effect of lurasidone on insulin resistance. In contrast, olanzapine demonstrated dose-dependent and potent glucose intolerance, and insulin resistance in both tests. Thus, in preclinical models, lurasidone demonstrates mild metabolic liability compared to existing SGAs such as olanzapine. However, confirmation of these effects in humans with equivalent tests should be confirmed. Public Library of Science 2014-09-25 /pmc/articles/PMC4177840/ /pubmed/25254366 http://dx.doi.org/10.1371/journal.pone.0107116 Text en © 2014 Wu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wu, Claire
Yuen, Jessica
Boyda, Heidi N.
Procyshyn, Ric M.
Wang, Cathy K.
Asiri, Yahya I.
Pang, Catherine C. Y.
Honer, William G.
Barr, Alasdair M.
An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine
title An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine
title_full An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine
title_fullStr An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine
title_full_unstemmed An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine
title_short An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine
title_sort evaluation of the effects of the novel antipsychotic drug lurasidone on glucose tolerance and insulin resistance: a comparison with olanzapine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177840/
https://www.ncbi.nlm.nih.gov/pubmed/25254366
http://dx.doi.org/10.1371/journal.pone.0107116
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