Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors.
Inhibitory neurosteroids
These neurosteroids exert inhibitory actions on neurotransmission. They act as positive allosteric modulators of the GABAA receptor (especially δ subunit-containing isoforms), and possess, in no particular order, antidepressant, anxiolytic, stress-reducing, rewarding,[10] prosocial,[11] antiaggressive,[12] prosexual,[11] sedative, pro-sleep,[13] cognitive and memory-impairing,[citation needed] analgesic,[14] anesthetic, anticonvulsant, neuroprotective, and neurogenic effects.[3]
Major examples include tetrahydrodeoxycorticosterone (THDOC), the androstane 3α-androstanediol, the cholestane cholesterol and the pregnanes pregnanolone (eltanolone), allopregnanolone (3α,5α-THP).[15][16]
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).
Neurosteroids such as DHEA and allopregnanolone.
