Department of Medical Chemistry, Molecular Biology and Pathobiochemistry Semmelweis University Budapest, Budapest, Hungary.
Pathol Oncol Res. 2012 Oct;18(4):1071-6. doi: 10.1007/s12253-012-9546-4. Epub 2012 Jun 30.
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.
非典型抗精神病药物（AAPD）被广泛用于治疗严重的精神疾病，具有明确的代谢副作用，如葡萄糖代谢紊乱、胰岛素抵抗和体重增加。研究表明，具有胰岛素增敏活性的羟胺衍生物 BGP-15 可预防脂肪细胞培养中 AAPD 引起的脂肪堆积，以及动物实验和健康志愿者中的胰岛素抵抗。本研究旨在比较 BGP-15 与传统口服降糖药对 AAPD 代谢副作用的预防作用。我们发现，BGP-15 不属于传统的胰岛素增敏剂或口服降糖药，它能够对抗抗精神病药物引起的大鼠胰岛素抵抗和体重增加，而罗格列酮和二甲双胍在应用剂量下没有效果。我们的结果证实，BGP-15 是一种有前途的新型候选药物，可控制非典型抗精神病药物的代谢副作用。研究数据表明，该大鼠模型适用于分析 AAPD 的代谢副作用和 BGP-15 的保护机制。
