Biosynthesis, mechanism of action, and clinical mportance of neuroactive steroids: Pearls from literature

Abstract

Aim: To review the biosynthesis, mechanism, and important effects of neurosteroids on brain functions and brain disease by modulating synaptic and extrasynaptic transmission. Materials and Methods: This article is based on a comprehensive database search on the internet. Full-text articles in English, published between 2001 and 2012, were searched for, using the terms 'neuroactive steroids', 'neurotransmitter agents', 'molecular mechanism', 'depression', 'anxiety' 'neuropsychopharmacology', 'interactions with receptors', 'neuroprotection', and 'neuroendocrinology' to identify potential therapeutic targets. The reference lists of leading review articles identified during this search were checked for additional publications. Results: Neurosteroids regulate physiological functions of the central nervous system (CNS) and help in the neurodevelopmental functions relating to their neuroprotective effects in brain injury and possible therapeutic potential in brain lesions and other diseases of the nervous system. Neurosteroids have been shown to affect neuronal excitability via their interaction with the ligand-gated ion channel family, such as the GABA A and 5-HT 3 receptors, by acting genomically as well as nongenomically. By virtue of these properties, neurosteroids appear to be relevant to pathophysiology and pharmacological treatment of many psychiatric disorders, including not only the notable mood and anxiety disorders, but also psychotic disorders, childhood dementia and stress disorders. They have also been found to be involved in the pathophysiology and treatment of epilepsy, alcohol and substance abuse. Conclusion: Neurosteroids may become potential targets for pharmacological intervention in the future, with further research at the basic science level as well as in the context of large double-blinded placebo-controlled investigations to elicit their role fully in the understanding and management of various psychiatric conditions.