• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of sexual medicine >Multifunctional pharmacology of flibanserin: possible mechanism of therapeutic action in hypoactive sexual desire disorder.
【24h】

Multifunctional pharmacology of flibanserin: possible mechanism of therapeutic action in hypoactive sexual desire disorder.

机译：氟班色林的多功能药理作用：性欲减退的治疗作用的可能机制。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

INTRODUCTION: Flibanserin is a novel pharmacologic agent in late-stage clinical testing for hypoactive sexual desire disorder (HSDD) in premenopausal women. AIM: The aim of this article is to review the hypothetical mechanism of action of flibanserin in HSDD. METHODS: A literature review was conducted of all published works on flibanserin and on related studies of serotonin (5-HT)(1A) receptors and 5-HT(2A) receptors, including their actions on monoamines and on sexual function. MAIN OUTCOME MEASURES: The main outcome measures are preclinical pharmacologic actions, especially changes in regional monoamines following treatment with flibanserin. RESULTS: At clinically relevant doses, flibanserin acts predominantly at 5-HT(1A) receptors as an agonist and secondarily at 5-HT(2A) receptors as an antagonist. Additional binding actions within an order of magnitude of its 5-HT(1A) affinity, which are not likely to be clinically relevant, include weaker antagonist actions at 5-HT(2C) and 5-HT(2B) receptors, and less defined activity at dopamine (DA) D4 receptors. The 5-HT(1A) actions of flibanserin are only seen postsynaptically, which is unlike other agents such as buspirone that act at presynaptic 5-HT(1A) receptors. Furthermore, the postsynaptic actions of chronic flibanserin administration appear to demonstrate a preference for some populations of postsynaptic 5-HT receptors, particularly those that are located on the prefrontal cortex (PFC) pyramidal neurons, which regulate monoamine release in certain selective brain regions. CONCLUSIONS: The regional selectivity of flibanserin results in a unique pattern of monoamine modulation. Sustained increases in baseline of DA and norepinephrine (NE) are observed in the PFC, and flibanserin dosing increases DA and NE levels above the basal changes. Conversely, flibanserin induces transient decreases in 5-HT levels in some brain areas such as the PFC, nucleus accumbens, and hypothalamus, but not in other brain areas such as the hippocampus. Therefore, since DA and NE are excitatory and 5-HT is inhibitory to sexual desire and arousal, it is tempting to postulate that the actions of flibanserin on serotonin receptors at the PFC pyramidal neurons, resulting in increased DA and NE yet reduced 5-HT in the PFC, are the mechanistic underpinnings of enhancing sexual desire in HSDD.
机译：氟班色林是绝经前妇女性欲减退（HSDD）后期临床测试中的新型药物。目的：本文的目的是审查氟班色林在HSDD中作用的假想机制。方法：对氟班色林以及5-羟色胺（5-HT）（1A）受体和5-HT（2A）受体的相关研究的所有已发表著作进行了文献综述，包括它们对单胺和性功能的作用。主要观察指标：主要观察指标是临床前药理作用，尤其是氟班色林治疗后局部单胺类药物的变化。结果：在临床相关剂量下，氟班色林主要作为激动剂作用于5-HT（1A）受体，其次作为拮抗剂作用于5-HT（2A）受体。在其5-HT（1A）亲和力的一个数量级内的其他结合作用，在临床上不太可能相关，包括对5-HT（2C）和5-HT（2B）受体的拮抗作用较弱，且定义较差多巴胺（DA）D4受体的活性。氟班色林的5-HT（1A）作用仅在突触后才能观察到，这与其他药物（如丁螺环酮）对突触前的5-HT（1A）受体起作用不同。此外，长期给予氟班色林的突触后作用似乎显示出对某些突触后5-HT受体群体的偏爱，尤其是那些位于额叶前皮质（PFC）锥体神经元上的受体，这些受体调节某些选择性大脑区域中的单胺释放。结论：氟班色林的区域选择性导致单胺调节的独特模式。在PFC中观察到DA和去甲肾上腺素（NE）的基线持续增加，而氟班色林的剂量使DA和NE的水平增加至基础水平以上。相反，氟班色林在某些大脑区域（例如PFC，伏隔核和下丘脑）引起5-HT含量的短暂降低，但在其他大脑区域（例如海马体）则不会。因此，由于DA和NE具有兴奋性，而5-HT抑制性欲和唤醒，因此很容易推测氟班色林对PFC锥体神经元的5-羟色胺受体的作用，导致DA和NE升高而5-HT降低在PFC中，是在HSDD中增强性欲的机制基础。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号