Neurosteroids: endogenous role in the human brain and therapeutic potentials

Prog Brain Res. 2010;186:113-37. doi: 10.1016/B978-0-444-53630-3.00008-7.


This chapter provides an overview of neurosteroids, especially their impact on the brain, sex differences and their therapeutic potentials. Neurosteroids are synthesized within the brain and rapidly modulate neuronal excitability. They are classified as pregnane neurosteroids, such as allopregnanolone and allotetrahydrodeoxycorticosterone, androstane neurosteroids, such as androstanediol and etiocholanolone, and sulfated neurosteroids such as pregnenolone sulfate. Neurosteroids such as allopregnanolone are positive allosteric modulators of GABA-A receptors with powerful anti-seizure activity in diverse animal models. Neurosteroids increase both synaptic and tonic inhibition. They are endogenous regulators of seizure susceptibility, anxiety, and stress. Sulfated neurosteroids such as pregnenolone sulfate, which are negative GABA-A receptor modulators, are memory-enhancing agents. Sex differences in susceptibility to brain disorders could be due to neurosteroids and sexual dimorphism in specific structures of the human brain. Synthetic neurosteroids that exhibit better bioavailability and efficacy and drugs that enhance neurosteroid synthesis have therapeutic potential in anxiety, epilepsy, and other brain disorders. Clinical trials with the synthetic neurosteroid analog ganaxolone in the treatment of epilepsy have been encouraging. Neurosteroidogenic agents that lack benzodiazepine-like side effects show promise in the treatment of anxiety and depression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Androstane-3,17-diol / biosynthesis*
  • Androstane-3,17-diol / pharmacology
  • Androstane-3,17-diol / therapeutic use
  • Anesthetics / pharmacology
  • Anesthetics / therapeutic use
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Brain / metabolism*
  • Brain / physiopathology*
  • Depression / drug therapy
  • Depression / metabolism
  • Female
  • Humans
  • Male
  • Neurotransmitter Agents / biosynthesis*
  • Neurotransmitter Agents / pharmacology
  • Neurotransmitter Agents / therapeutic use
  • Pregnanolone / analogs & derivatives
  • Pregnanolone / biosynthesis*
  • Pregnanolone / pharmacology
  • Pregnanolone / therapeutic use
  • Premenstrual Syndrome / drug therapy
  • Premenstrual Syndrome / metabolism
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology
  • Seizures / drug therapy
  • Seizures / metabolism
  • Sex Characteristics*
  • Stress, Physiological / drug effects


  • Anesthetics
  • Neurotransmitter Agents
  • Receptors, GABA-A
  • Androstane-3,17-diol
  • ganaxolone
  • Pregnanolone