Effects of 3α-Amino-5α-pregnan-20-one on GABAA Receptor: Synthesis, Activity and Cytotoxicity

Abstract

The 3α-hydroxy function has been considered essential for the biological activity of neurosteroids at the GABAA receptor. It was found that 3α-amino-5α-pregnan-20-one (3) increased the binding of [3H]flunitrazepam at the GABAA receptor in the primary culture of cortical neurons. This derivative did not display cytotoxicity at relevant neuroactive concentrations, and its structure enabled us to gain further insight into possible functional group modifications in position 3α. Various synthetic methods were investigated in search for the most suitable synthetic approach.