• DOI:10.1096/fasebj.6.6.1347506
• Corpus ID: 27623304

NEUROACTIVE STEROIDS

@article{Paul1993NEUROACTIVES,
  title={NEUROACTIVE STEROIDS},
  author={Steven M Paul},
  journal={Pediatric Research},
  year={1993},
  volume={33},
  pages={S9-S9}
}

• S. Paul
• Published 1 March 1992
• Biology, Medicine, Chemistry
• Pediatric Research

It is now well accepted that certain steroids rapidly alter the excitability of neurons via non-genomic mechanisms, resulting in behavioral effects within minutes following parenteral administration. Almost 50 years ago Selye first identified the sedative/anesthetic properties of pregnane and androstane steroids including the 3α-hydroxy A-ring reduced metabolites of progesterone and deoxycorticosterone, allopregnanolone and allotetrahydroDOC respectively. We have shown that these 3α-hydroxy A-ring reduced metabolites are potent ligands of central and peripheral GABAA receptors. Using biochemical and eleetrophysiological techniques we have shown that these steroids selectively augment the inhibitory properties of GABA by binding to sites that are distinct from those for barbiturates and benzodiazepines. We have termed these GABAA receptor-active steroids -- “neuroactive steroids.” The latter include any natural or synthetic steroid that rapidly alters the excitability of neurons. Some neuroactive steroids are also neurosteroids in that they are synthesized de novo within the CNS. Several neuroactive steroids have recently been shown to have excitatory properties, and some like the synthetic amidine steroid R5135 and pregnenolone sulfate antagonize GABA receptors. Pregnenolone sulfate has also recently been shown to augment the actions of glutamate at the NMDA receptor. Thus, steroids can rapidly modulate both inhibitory and excitatory neurotranemitters via direct interaction with their receptors. Examples of both inhibitory and excitatory neuroactive steroids will be presented as will a discussion of their pharmacological, physiological, and clinical significance.