Neurosteroids in Psychiatry – Pharmacology | Mechanisms of Action | Clinical Application

Posted on:March 19, 2022
Last Updated: November 10, 2023
Time to read: 17–21 minutes

Neurosteroids or Neuroactive Steroids (NAS) are endogenous steroid hormones synthesised from cholesterol in the mitochondria of glial cells or from steroid hormone precursors like progesterone that accumulate in the nervous system that act locally and rapidly to affect brain function and behaviour. [Baulieu 1997]

They influence neuronal excitability either by directly acting as transcriptional factors or via their non-genomic action on ion channels and cell receptors. [Truss and Beato 1993]

However, it is essential to note that neurosteroids do not interact with classical steroid hormone receptors. [Reddy 2003]

Neuroactive steroids refer to “any natural or synthetic steroid that rapidly alters neuronal excitability via non-genomic mechanisms.” [Paul and Purdy,1992]

  • Allopregnanolone (3α,5α-tetrahydroprogesterone; 3α,5α-THP) or referred to AlloP in this article.
  • Progesterone
  • Allopregnanedione (5α-dihydroprogesterone, 5α-DHP)
  • Tetrahydrodeoxycorticosterone (THDOC; 3α,5α- tetrahydrodeoxycorticosterone) / or allotetrahydrodeoxycorticosterone (ALLO-THDOC)
  • PregNANolone (3α,5β-tetrahydroprogesterone; 3α,5β- THP)
  • PregNENolone
  • PregNENolone sulfate (PS)
  • IsopregNANolone (3β,5α-tetrahydroprogesterone; 3β,5α-THP)
  • Estrogen
  • Dehydroepiandrosterone (DHEA; androstenolone) and DHEA sulfate
  • Estradiol
  • Vitamin D