title: A novel insulin sensitizer drug candidate-BGP-15-can prevent metabolic side effects of atypical antipsychotics.
abstract: Atypical antipsychotic drugs (AAPD) are widely used to treat severe psychiatric disorders, have well documented metabolic side effects such as disturbances in glucose metabolism, insulin resistance and weight gain. It has been shown that BGP-15, a hydroxylamine derivative with insulin sensitizing activity can prevent AAPD provoked fat accumulation in adipocyte cultures, and insulin resistance in animal experiments and in healthy volunteers. The aim of this study was to compare the preventive effect of BGP-15 with conventional oral antidiabetics on metabolic side effects of AAPDs. We found that BGP-15 that does not belong to either conventional insulin sensitizers or oral antidiabetics, is able to counteract insulin resistance and weight gain provoked by antipsychotic agents in rats while rosiglitazone and metformin were not effective in the applied doses. Our results confirm that BGP-15 is a promising new drug candidate to control the metabolic side effects of atypical antipsychotics. Data indicate that this rat model is suitable to analyze the metabolic side effects of AAPDs and the protective mechanism of BGP-15.
authors: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry Semmelweis University Budapest, Budapest, Hungary.
authors: Zsuzsanna
authors: Z
authors: Literati-Nagy
authors: Kálmán
authors: K
authors: Tory
authors: Botond
authors: B
authors: Literáti-Nagy
authors: Attila
authors: A
authors: Kolonics
authors: László
authors: L
authors: Vígh
authors: László
authors: L
authors: Vígh
authors: József
authors: J
authors: Mandl
authors: Zoltán
authors: Z
authors: Szilvássy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D015309:Glucose Clamp Technique; D007333:Insulin Resistance; D010091:Oximes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D010091:Oximes; D010880:Piperidines; D020011:Protective Agents; C405586:BGP 15