Antipsychotic induced metabolic abnormalities: an interaction study with various PPAR modulators in mice

Area of Science:

• Pharmacology
• Metabolic Disorders
• Neuroscience

Background:

• Antipsychotic medications are associated with metabolic disturbances, including abnormal glucose and lipid regulation.
• Hyperglycemia and hyperlipidemia are known side effects of certain antipsychotic drugs used to treat schizophrenia.

Purpose of the Study:

• To investigate the efficacy of peroxisome proliferator-activated receptor (PPAR) modulators in mitigating antipsychotic-induced metabolic abnormalities.
• To evaluate the effects of glimepiride, rosiglitazone, and fenofibrate on hyperglycemia and hyperlipidemia induced by chlorpromazine, clozapine, and ziprasidone in mice.

Main Methods:

• Male Swiss albino mice were administered chlorpromazine, clozapine, or ziprasidone concurrently with glimepiride, rosiglitazone, or fenofibrate for seven days.
• Plasma glucose, insulin, and triglyceride levels were measured at the study's conclusion.

Main Results:

• Chlorpromazine and clozapine increased glucose and triglyceride levels; ziprasidone elevated triglyceride and insulin levels.
• Glimepiride and rosiglitazone reduced glucose and triglyceride levels in mice treated with chlorpromazine and clozapine.
• Fenofibrate decreased glucose in clozapine-treated mice and triglyceride levels across all antipsychotic groups.
• All tested antidiabetic/hypolipidemic agents lowered triglyceride and insulin levels in ziprasidone-treated mice.

Conclusions:

• The study suggests that antipsychotic-induced metabolic dysregulation, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, may arise from varied underlying mechanisms.
• PPAR modulators demonstrate potential in managing specific metabolic side effects associated with different antipsychotic agents.