Neurosteroids in Psychiatry – Pharmacology | Mechanisms of Action | Clinical Application
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.
- Allopregnanedione (5α-dihydroprogesterone, 5α-DHP)
- Tetrahydrodeoxycorticosterone (THDOC; 3α,5α- tetrahydrodeoxycorticosterone) / or allotetrahydrodeoxycorticosterone (ALLO-THDOC)
- PregNANolone (3α,5β-tetrahydroprogesterone; 3α,5β- THP)
- PregNENolone sulfate (PS)
- IsopregNANolone (3β,5α-tetrahydroprogesterone; 3β,5α-THP)
- Dehydroepiandrosterone (DHEA; androstenolone) and DHEA sulfate
- Vitamin D
Motzo, C., Porceddu, M. L., Maira, G., Flore, G., Concas, A., Dazzi, L., & Biggio, G. (1996). Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone. Journal of Psychopharmacology, 10(4), 266-272.
Maki, P. M., Kornstein, S. G., Joffe, H., Bromberger, J. T., Freeman, E. W., Athappilly, G., … & Board of Trustees for The North American Menopause Society (NAMS) and the Women and Mood Disorders Task Force of the National Network of Depression Centers. (2019). Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Journal of women’s health, 28(2), 117-134.
Brown, E. S., Park, J., Marx, C. E., Hynan, L. S., Gardner, C., Davila, D., Nakamura, A., Sunderajan, P., Lo, A., & Holmes, T. (2014). A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 39(12), 2867–2873.