1. A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models.
- Author
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Boyda HN, Procyshyn RM, Tse L, Yuen JWY, Honer WG, and Barr AM
- Subjects
- Animals, Female, Glucose Clamp Technique, Glucose Tolerance Test, Metabolic Diseases chemically induced, Models, Animal, Rats, Rats, Sprague-Dawley, Antipsychotic Agents toxicity, Insulin Resistance, Metabolic Diseases pathology, Paliperidone Palmitate toxicity, Risperidone toxicity
- Abstract
Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: WGH has received consulting fees or sat on paid advisory boards for Otsuka/Lundbeck, Newron, AlphaSights, Guidepoint, Translational Life Sciences and holds shares in Translational Life Sciences and Eli Lilly. He was additionally supported by the Jack Bell Chair in Schizophrenia. RMP has been a member of the following advisory boards in the past 3 years: Janssen, Lundbeck, and Otsuka; a member of the following speaker’s bureaus in the past 3 years: Janssen, Lundbeck, and Otsuka; and received grants from the Canadian Institutes of Health Research. All other authors declare that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2021
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