Realizing the Therapeutic Potential of Neuroactive Steroid Modulators of the GABAA Receptor

The document from May 1, 2020, reviews the therapeutic potential of neuroactive steroids, particularly as modulators of the GABA_A receptor, for treating various psychiatric and neurological disorders. It discusses the history of neuroactive steroids, their clinical applications, and the challenges faced in developing them as medicines. The FDA's approval of allopregnanolone (brexanolone) for postpartum depression has sparked renewed interest in this research area. The review also examines the potential of neuroactive steroids in treating conditions like anxiety, pain, Alzheimer's disease, and other neurodegenerative disorders, and the development of non-steroidal compounds, such as 2-261 and 2-329, which act as positive allosteric modulators of GABA_A receptors. These non-steroidal small molecules show promise in retaining the therapeutic effects of neurosteroids without their side effects, potentially leading to more effective drug development. The research on these compounds was supported by grants from the National Institute of Neurological Disorders and Stroke and the Wellbeing of Women.