Synthetic neurosteroids on brain protection  

作　　者：Mariana Rey Héctor Coirini 

机构地区：[1]Laboratorio de Neurobiología,Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, (C1428ADN) Ciudad Autónoma de Buenos Aires,Argentina [2]Departamento de Bioquímica Humana,Facultad de Medicina,Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires,Argentina

出　　处：《Neural Regeneration Research》2015年第1期17-21,共5页中国神经再生研究（英文版）

基　　金：supported by grants from Agencia Nacional de Promocion Cientifica y Tecnologica(ANPCYT,PICT-2006-727);Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET,PIP-860)

摘　　要：Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids adminis- tration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute prom- ising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3ct-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids adminis- tration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute prom- ising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3ct-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.

关 键 词：ALLOPREGNANOLONE synthetic steroids GABAA receptor NEUROPROTECTION cerebral cortex HIPPOCAMPUS 

分 类 号：R971[医药卫生—药品]