Abstract
The term “neuroactive steroid” (NAS) refers to steroids which, independent of their origin, are capable of modifying neural activities. These steroids positively or negatively modulate the function of members of the ligand-gated ion channel superfamily. Those with positive allosteric actions on the γ-amino butyric acid type A receptor (GABAA receptor) have been shown to be potent anticonvulsants, anxiolytics, and antistress agents and to possess sedative, hypnotic, and anesthetic activities. New types of neuroactive steroids have been widely sought and structural modifications of the naturally occurring metabolites allopregnanolone, pregnanolone and allotetrahydrodeoxycorticosterone, have been examined in the light of the vast family of GABA receptor subtypes within the brain. Here we review the structure-activity relationship (SAR) of neuroactive steroid analogues obtained by modification of the steroid nucleus, including substitutions at the A, B, C, and D rings and the side chain, with emphasis on the different pharmacophores proposed.
Keywords: Neuroactive steroids, neurosteroids, structure-activity relationship, GABAA receptor, anticonvulsant
Current Medicinal Chemistry
Title: Structure-Activity Relationships of Neuroactive Steroids Acting on the GABAA Receptor
Volume: 16 Issue: 4
Author(s): Adriana S. Veleiro and Gerardo Burton
Affiliation:
Keywords: Neuroactive steroids, neurosteroids, structure-activity relationship, GABAA receptor, anticonvulsant
Abstract: The term “neuroactive steroid” (NAS) refers to steroids which, independent of their origin, are capable of modifying neural activities. These steroids positively or negatively modulate the function of members of the ligand-gated ion channel superfamily. Those with positive allosteric actions on the γ-amino butyric acid type A receptor (GABAA receptor) have been shown to be potent anticonvulsants, anxiolytics, and antistress agents and to possess sedative, hypnotic, and anesthetic activities. New types of neuroactive steroids have been widely sought and structural modifications of the naturally occurring metabolites allopregnanolone, pregnanolone and allotetrahydrodeoxycorticosterone, have been examined in the light of the vast family of GABA receptor subtypes within the brain. Here we review the structure-activity relationship (SAR) of neuroactive steroid analogues obtained by modification of the steroid nucleus, including substitutions at the A, B, C, and D rings and the side chain, with emphasis on the different pharmacophores proposed.
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Cite this article as:
Veleiro S. Adriana and Burton Gerardo, Structure-Activity Relationships of Neuroactive Steroids Acting on the GABAA Receptor, Current Medicinal Chemistry 2009; 16 (4) . https://dx.doi.org/10.2174/092986709787315522
DOI https://dx.doi.org/10.2174/092986709787315522 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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