Abstract

Neurosteroids are natural or synthetic steroid derivatives which act locally in brain by modulating neuronal excitability. By binding to a specific site on the GABA-A receptor, neurosteroids function as modulators of either excitatory or inhibitory response. These agents can be utilised in therapy of various neurological and psychiatric conditions including epilepsy, disorders of learning and memory, anxiety, stress, depression, schizophrenia and substance abuse. Progesterone derivatives have the potential for treating anxiety, depression, schizophrenia, alcoholism, and stress-related psychiatric disorders. However, due to hinderances such as low oral bioavailability, lack of specificity and activity at the steroid receptors in the periphery leading to unwanted effects, their use in clinical practice has limitations. To overcome this, synthetic derivatives of endogenous neurosteroids such as Brexanolone, Sepranolone, Ganaxolone and Alphaxalone are being developed which are expected to possess improved bioavailability, specificity and reduced unwanted effects. The field of neurosteroids as potential therapeutic agents in psychiatry is in its early stages but holds substantial promise. Development of synthetic analogues of neurosteroids with improved efficacy and safety if successful will revolutionize the clinical approach to the treatment of these complex neuropsychiatric conditions.

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