Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge


Structure-Activity Relationships of Neuroactive Steroids Acting on the GABAA Receptor

Author(s): Adriana S. Veleiro and Gerardo Burton

Affiliation: Departamento de Quimica Organica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.

Keywords: Neuroactive steroids, neurosteroids, structure-activity relationship, GABAA receptor, anticonvulsant


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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Article Details

Page: [455 - 472]
Pages: 18
DOI: 10.2174/092986709787315522