A parametric study of the acute effects of antipsychotic drugs on glucose sensitivity in an animal model

The therapeutic use of atypical antipsychotics is associated with a high incidence of metabolic side-effects. In the present study we examined the acute effects of both high and low-dose atypical antipsychotic drugs and one typical drug on alterations in glucose and insulin parameters using a rodent model. The effects of administration of clozapine (2 mg/kg; 20 mg/kg), olanzapine (1.5 mg/kg; 15 mg/kg), risperidone (0.5 mg/kg; 2.5 mg/kg) and haloperidol (0.1 mg/kg; 1.0 mg/kg) on glucose sensitivity and insulin resistance were determined through HOMA-IR values in fasted rats and glucose clearance during a glucose tolerance test. Acute effects were determined 60, 180 or 360 min following drug administration. The atypical antipsychotics produced significant dose and time dependent effects on fasting plasma glucose and insulin concentrations, HOMA-IR values, insulin resistance and glucose intolerance. The greatest effect on glucose dysregulation was noted primarily with clozapine and olanzapine; however, all four treatments caused significant increases in fasting glucose and/or insulin levels with the high dose, 60 min post-drug administration. Together, these findings indicate that acute administration of antipsychotic drugs has potent effects on metabolic regulation of glucose and insulin sensitivities, which may contribute to metabolic side-effects seen in humans. (C) 2010 Elsevier Inc. All rights reserved.