The translocator protein (TSPO), also initially described as the peripheral benzodiazepine receptor (PBR), is a mitochondrialprotein that is involved in neurosteroid biosynthesis.[12][13] It is activated by certain benzodiazepines such as diazepam and midazolam, and via this action, inhibitory neurosteroid levels are increased.[1][12][13] Selective TSPO activators, such as emapunil, are under investigation for clinical use as possible anxiolytics.[1]
Progesterone, which is the endogenous precursor to the inhibitory neurosteroids 5α-dihydroprogesterone and allopregnanolone, as well as, more distantly, THDOC,[1][14] when administered exogenously, has been found to behave as a prodrug to these neurosteroids,[15][16] with clinical signs of their action, such as sedation, readily evident in humans.[17][18][19] Exogenous pregnenolone has similarly been found to act as a prodrug of allopregnanolone.[20]
Paracetamol (acetaminophen; Tylenol) has been shown to act at SULT2A1 (and potentially at SULT2B1) as an inhibitor of neurosteroidogenesis.[22] Specifically, the production of sulfate-containing neurosteroids, such as DHEA-S and pregnenolone sulfate, were decreased in patients taking paracetamol.[22]
^Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R (March 2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity". Mol. Psychiatry. 11 (3): 261–72. doi:10.1038/sj.mp.4001782. PMID16344854. S2CID21473462.
^Civic D, Scholes D, Ichikawa L, et al. (June 2000). "Depressive symptoms in users and non-users of depot medroxyprogesterone acetate". Contraception. 61 (6): 385–90. doi:10.1016/s0010-7824(00)00122-0. PMID10958882.
^ abTvrdeić A, Poljak L (2016). "Neurosteroids, GABAA receptors and neurosteroid based drugs: are we witnessing the dawn of the new psychiatric drugs?". Endocrine Oncology and Metabolism. 2 (1): 60–71. doi:10.21040/eom/2016.2.7 (inactive 2024-04-06). ISSN1849-8922.{{cite journal}}: CS1 maint: DOI inactive as of April 2024 (link)
^ abPapadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapère JJ, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang MR, Gavish M (August 2006). "Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function". Trends Pharmacol. Sci. 27 (8): 402–9. doi:10.1016/j.tips.2006.06.005. PMID16822554.
^Söderpalm AH, Lindsey S, Purdy RH, Hauger R, Wit de H (2004). "Administration of progesterone produces mild sedative-like effects in men and women". Psychoneuroendocrinology. 29 (3): 339–54. doi:10.1016/s0306-4530(03)00033-7. PMID14644065. S2CID21796848.
^de Wit H, Schmitt L, Purdy R, Hauger R (2001). "Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women". Psychoneuroendocrinology. 26 (7): 697–710. doi:10.1016/s0306-4530(01)00024-5. PMID11500251. S2CID20611661.
^Schmoutz CD, Guerin GF, Goeders NE (2014). "Role of GABA-active neurosteroids in the efficacy of metyrapone against cocaine addiction". Behav. Brain Res. 271: 269–76. doi:10.1016/j.bbr.2014.06.032. PMID24959859. S2CID37159095.