Excitatory neurosteroids

These neurosteroids have excitatory effects on neurotransmission. They act as potent negative allosteric modulators of the GABAA receptor, weak positive allosteric modulators of the NMDA receptor, and/or agonists of the σ1 receptor, and mostly have antidepressant, anxiogenic, cognitive and memory-enhancing, convulsant, neuroprotective, and neurogenic effects. Major examples include the pregnanes pregnenolone sulfate (PS), epipregnanolone, and isopregnanolone (sepranolone), the androstanes dehydroepiandrosterone (DHEA; prasterone), and dehydroepiandrosterone sulfate (DHEA-S; prasterone sulfate), and the cholestane 24(S)-hydroxycholesterol (NMDA receptor-selective; very potent).

• Pregnenolone alone.
• Pregnanolone binds beta3-alpha5 GABAA receptor (5o8f).
• Pregnanolone binding site is situated between 2 monomers.