A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models.
<h4>Background</h4>The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0246211 |
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| author | Heidi N Boyda Ric M Procyshyn Lurdes Tse Jessica W Y Yuen William G Honer Alasdair M Barr |
| author_facet | Heidi N Boyda Ric M Procyshyn Lurdes Tse Jessica W Y Yuen William G Honer Alasdair M Barr |
| author_sort | Heidi N Boyda |
| collection | DOAJ |
| description | <h4>Background</h4>The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone (9-hydroxyrisperidone) are two commonly used antipsychotic drugs with moderate metabolic liability. However, there is a dearth of preclinical data that directly compares the metabolic effects of these two drugs, using sophisticated experimental procedures. The goal of the present study was to compare metabolic effects for each drug versus control animals.<h4>Methods</h4>Adult female rats were acutely treated with either risperidone (0.1, 0.5, 1, 2, 6 mg/kg), paliperidone (0.1, 0.5, 1, 2, 6 mg/kg) or vehicle and subjected to the glucose tolerance test; plasma was collected to measure insulin levels to measure insulin resistance with HOMA-IR. Separate groups of rats were treated with either risperidone (1, 6 mg/kg), paliperidone (1, 6 mg/kg) or vehicle, and subjected to the hyperinsulinemic euglycemic clamp.<h4>Results</h4>Fasting glucose levels were increased by all but the lowest dose of risperidone, but only with the highest dose of paliperidone. HOMA-IR increased for both drugs with all but the lowest dose, while the three highest doses decreased glucose tolerance for both drugs. Risperidone and paliperidone both exhibited dose-dependent decreases in the glucose infusion rate in the clamp, reflecting pronounced insulin resistance.<h4>Conclusions</h4>In preclinical models, both risperidone and paliperidone exhibited notable metabolic side-effects that were dose-dependent. Differences between the two were modest, and most notable as effects on fasting glucose. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T19:27:48Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-395733b38f474936b75a224d3daac1c02022-12-21T21:35:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01161e024621110.1371/journal.pone.0246211A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models.Heidi N BoydaRic M ProcyshynLurdes TseJessica W Y YuenWilliam G HonerAlasdair M Barr<h4>Background</h4>The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone (9-hydroxyrisperidone) are two commonly used antipsychotic drugs with moderate metabolic liability. However, there is a dearth of preclinical data that directly compares the metabolic effects of these two drugs, using sophisticated experimental procedures. The goal of the present study was to compare metabolic effects for each drug versus control animals.<h4>Methods</h4>Adult female rats were acutely treated with either risperidone (0.1, 0.5, 1, 2, 6 mg/kg), paliperidone (0.1, 0.5, 1, 2, 6 mg/kg) or vehicle and subjected to the glucose tolerance test; plasma was collected to measure insulin levels to measure insulin resistance with HOMA-IR. Separate groups of rats were treated with either risperidone (1, 6 mg/kg), paliperidone (1, 6 mg/kg) or vehicle, and subjected to the hyperinsulinemic euglycemic clamp.<h4>Results</h4>Fasting glucose levels were increased by all but the lowest dose of risperidone, but only with the highest dose of paliperidone. HOMA-IR increased for both drugs with all but the lowest dose, while the three highest doses decreased glucose tolerance for both drugs. Risperidone and paliperidone both exhibited dose-dependent decreases in the glucose infusion rate in the clamp, reflecting pronounced insulin resistance.<h4>Conclusions</h4>In preclinical models, both risperidone and paliperidone exhibited notable metabolic side-effects that were dose-dependent. Differences between the two were modest, and most notable as effects on fasting glucose.https://doi.org/10.1371/journal.pone.0246211 |
| spellingShingle | Heidi N Boyda Ric M Procyshyn Lurdes Tse Jessica W Y Yuen William G Honer Alasdair M Barr A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models. PLoS ONE |
| title | A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models. |
| title_full | A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models. |
| title_fullStr | A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models. |
| title_full_unstemmed | A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models. |
| title_short | A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models. |
| title_sort | comparison of the metabolic side effects of the second generation antipsychotic drugs risperidone and paliperidone in animal models |
| url | https://doi.org/10.1371/journal.pone.0246211 |
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