Neurosteroids: endogenous role in the human brain and therapeutic potentials.
Neurosteroids: endogenous role in the human brain and therapeutic potentials.
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DOI：
10.1016/b978-0-444-53630-3.00008-7
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发表时间：
2010
影响因子：
--
通讯作者：
Reddy, Doodipala Samba
中科院分区：
文献类型：
--
作者：
Reddy, Doodipala Samba
关键词：
本章概述了神经类固醇，特别是它们对大脑的影响，性别差异和治疗潜力。神经类固醇在脑内合成并快速调节神经元兴奋性。它们被分类为甾烷类神经甾体，如别孕烯醇酮和别四氢脱氧皮质酮，以及雄甾烷类神经甾体，如雄甾烷酮和乙胆烷酮。神经甾体如别孕烯醇酮是GABA-A受体的正变构调节剂，在多种动物模型中具有强大的抗癫痫活性。神经类固醇增加突触和紧张性抑制。它们是癫痫易感性、焦虑和压力的内源性调节剂。硫酸化神经甾体如硫酸双烯醇酮是负性GABA-A受体调节剂，是记忆增强剂。大脑疾病易感性的性别差异可能是由于神经类固醇和人类大脑特定结构的性别二型性。具有更好的生物利用度和功效的合成神经类固醇以及增强神经类固醇合成的药物在焦虑症、癫痫和其他脑部疾病中具有治疗潜力。用合成神经类固醇类似物加奈索酮治疗癫痫的临床试验令人鼓舞。没有苯二氮卓类副作用的神经类固醇生成剂在治疗焦虑和抑郁方面显示出希望。
This chapter provides an overview of neurosteroids, especially their impact on the brain, sex differences and therapeutic potentials. Neurosteroids are synthesized within the brain and rapidly modulate neuronal excitability. They are classified as pregnane neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone, and androstane neurosteroids, such as androstanediol and etiocholanone. Neurosteroids such as allopregnanolone are positive allosteric modulators of GABA-A receptors with powerful antiseizure activity in diverse animal models. Neurosteroids increases both synaptic and tonic inhibition. They are endogenous regulators of seizure susceptibility, anxiety and stress. Sulfated neurosteroids such as pregnenolone sulfate, which are negative GABA-Areceptor modulators, are memory-enhancing agents. Sex differences in susceptibility to brain disorders could be due to neurosteroids and sexual dimorphism in specific structures of the human brain. Synthetic neurosteroids that exhibit better bioavailability and efficacy and drugs that enhance neurosteroid synthesis have therapeutic potential in anxiety, epilepsy and other brain disorders. Clinical trials with the synthetic neurosteroid analog ganaxolone in the treatment of epilepsy have been encouraging. Neurosteroidogenic agents that lack benzodiazepine-like side effects show promise in the treatment of anxiety and depression.