[11][6] Side effects of brexanolone may include sedation, sleepiness, dry mouth, hot flashes, and loss of consciousness.
[6][11] It is a neurosteroid and acts as a positive allosteric modulator of the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).
[17] Brexanolone is used to treat postpartum depression in adult women, administered as a continuous intravenous infusion over a period of 60 hours, and essential tremor.
[11][18] Women experiencing moderate to severe postpartum depression when treated with a single dose of intravenous brexanolone display a significant reduction in HAM-D scores which persisted 30 days post-treatment.
[19] Side effects of brexanolone include dizziness (10–20%), sedation (13–21%), headache (18%), nausea (10%), dry mouth (3–11%), loss of consciousness (3–5%), and flushing (2–5%).
[6] Serious or severe adverse effects are rare but may include altered state of consciousness, syncope, presyncope, fatigue, and insomnia.
[10] Fluctuations in the levels of allopregnanolone and the other neurosteroids seem to play an important role in the pathophysiology of mood, anxiety, premenstrual syndrome, catamenial epilepsy, and various other neuropsychiatric conditions.
[10] It is made from pregnenolone, and is a positive allosteric modulator of the action of γ-aminobutyric acid (GABA) at GABAA receptor.
[10] Allopregnanolone has effects similar to those of other positive allosteric modulators of the GABA action at GABAA receptor such as the benzodiazepines, including anxiolytic, sedative, and anticonvulsant activity.
[35] Allopregnanolone has also been found to act as a positive allosteric modulator of the GABAA-ρ receptor, though the implications of this action are unclear.
[39] Along with the other inhibitory neurosteroids, allopregnanolone appears to have little or no action at other ligand-gated ion channels, including the NMDA, AMPA, kainate, and glycine receptors.
[40][46] Similarly to many other GABAA receptor positive allosteric modulators, allopregnanolone has been found to act as an inhibitor of L-type voltage-gated calcium channels (L-VGCCs),[47] including α1 subtypes Cav1.2 and Cav1.3.
[49] Increased levels of allopregnanolone can produce paradoxical effects, including negative mood, anxiety, irritability, and aggression.
[50][51][52] This appears to be because allopregnanolone possesses biphasic, U-shaped actions at the GABAA receptor – moderate level increases (in the range of 1.5–2 nmol/L total allopregnanolone, which are approximately equivalent to luteal phase levels) inhibit the activity of the receptor, while lower and higher concentration increases stimulate it.
[54] Other GABAA receptor PAMs, such as benzodiazepines, are not thought of as antidepressants and have no proven efficacy,[54] although alprazolam has historically been prescribed for depression.
[54] It is possible that neurosteroids like allopregnanolone may act on other targets, including membrane progesterone receptors, T-type voltage-gated calcium channels, and others, to mediate antidepressant effects.
[63] As a result, there has been some interest in using oral progesterone to treat catamenial epilepsy,[64] as well as other menstrual cycle-related and neurosteroid-associated conditions.