Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio.

IF 2.9 3区医学 Q2 Medicine

BMC Pharmacology & Toxicology Pub Date : 2012-06-22 DOI:10.1186/1471-2210-12-8

Somayeh Jafari, Marc E Bouillon, Xu-Feng Huang, Stephen G Pyne, Francesca Fernandez-Enright

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引用次数: 16

Abstract

Background: Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios.

Results: We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors.

Conclusions: We suggest that thienobenzodiazepines 8b and 8c with lower binding affinity for the H1 receptors, but similar 5HT2A/D2 receptor binding affinity ratios to those of olanzapine. These compounds may offer a better pharmacological profile than olanzapine for treating patients with schizophrenia.

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新型奥氮平类似物显示H1受体亲和力降低，并保留5HT2A/D2结合亲和力比。

背景:奥氮平是一种临床疗效高的非典型抗精神病药物，但治疗后患者会出现严重的体重增加和代谢紊乱。阻断组胺1 (H1)受体被认为在奥氮平诱导的体重增加中起着至关重要的作用，而这种药物的治疗效果主要归功于其有利的5 -羟色胺能2A和多巴胺2 (5HT2A/D2)受体结合亲和力比。结果:我们合成了新的奥氮平类似物8a和8b以及已知的衍生物8c，并分别检测了它们对5HT2A、D2和H1受体的体外亲和力。结论:我们认为噻吩苯二氮卓类药物8b和8c对H1受体的结合亲和力较低，但对5HT2A/D2受体的结合亲和力与奥氮平相似。这些化合物在治疗精神分裂症患者方面可能比奥氮平具有更好的药理作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACY-TOXICOLOGY

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.