GABAA receptor
The mechanism by which neurosteroid GABAA receptor PAMs like brexanolone have antidepressant effects is unknown. Other GABAA receptor PAMs, such as benzodiazepines, are not thought of as antidepressants and have no proven efficacy, despite clinicians prescribing Alprazolam for depression in the past. Neurosteroid GABAA receptor PAMs are known to interact with GABAA receptors and sub-populations differently than benzodiazepines. As examples, GABAA receptor-potentiating neurosteroids may preferentially target δ subunit-containing GABAA receptors, and enhance both tonic and phasic inhibition mediated by GABAA receptors. It is also 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.