Collect. Czech. Chem. Commun. 2004, 69, 1506-1516

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

Libor Matyáša, Alexander Kasala,*, Zoila Babot Rierab and Cristina E. Sunolb

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
b Departament de Neuroquímica, Institut d'Investigacions Biomédiques de Barcelona, CSIC (IDIBAPS), E-08036 Barcelona, Spain


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.

Keywords: GABAA receptor; Steroids; Neurosteroids; Allopregnanolone; [3H]Flunitrazepam; 3α-Amino-5α-pregnan-20-one; Cytotoxicity; MoO3.

References: 36 live references.