| IUPAC name
| Other names
Isoallopregnanolone, epiallopregnanolone, sepranolone, 3β,5α-tetrahydroprogesterone
|3D model (Jmol)||Interactive image|
|Molar mass||318.49 g/mol|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Isopregnanolone, also known as isoallopregnanolone and epiallopregnanolone, as well as sepranolone (INN), and as 3β-hydoxy-5α-pregnan-20-one or 3β,5α-tetrahydroprogesterone (3β,5α-THP), is an endogenous neurosteroid and a natural 3β-epimer of allopregnanolone. It has been reported to act as a subunit-selective negative allosteric modulator of the GABAA receptor, and antagonizes in animals and humans some but not all of the GABAA receptor-mediated effects of allopregnanolone, such as anesthesia, sedation, and reduced saccadic eye movements, but not learning impairment. Isopregnanolone has no hormonal effects and appears to have no effect on the GABAA receptor by itself; it selectively antagonizes allopregnanolone and does not affect the effects of other types of GABAA receptor positive allosteric modulators such as benzodiazepines or barbiturates.
Isopregnanolone is synthesized from progesterone in the body by the actions of the enzymes 5α-reductase and 3β-hydroxysteroid dehydrogenase (with 5α-dihydroprogesterone as the intermediate in this two-step transformation) and can be reversibly metabolized into allopregnanolone by the enzyme 3α-hydroxysteroid dehydrogenase. Levels of isopregnanolone, progesterone, and allopregnanolone are highly correlated across the menstrual cycle and throughout pregnancy. The concentrations of isopregnanolone are significantly less than those of progesterone and allopregnanolone; about half of those of allopregnanolone, to be precise. Isopregnanolone has a relatively long serum half-life of 14 hours in humans.
- Hedström H, Bixo M, Nyberg S, Spigset O, Zingmark E, Bäckström T (2009). "Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women". Psychopharmacology (Berl.). 203 (1): 85–98. doi:10.1007/s00213-008-1372-8. PMID 18949461.
- Öfverman, C., Strömberg, J., Birzniece, V., Turkmen, S., Hill, M., Lundgren, P., ... & Johansson, I. M. (2009). The progesterone metabolite isoallopregnanolone is a subunit-selective antagonist of the GABA-A receptor. Chicago
- Bäckström T, Wahlström G, Wahlström K, Zhu D, Wang MD (2005). "Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats". Eur. J. Pharmacol. 512 (1): 15–21. doi:10.1016/j.ejphar.2005.01.049. PMID 15814085.
- Bengtsson SK, Nyberg S, Hedström H, Zingmark E, Jonsson B, Bäckström T, et al. (2015). "Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans". Psychoneuroendocrinology. 52: 22–31. doi:10.1016/j.psyneuen.2014.10.025. PMID 25459890.
- Lundgren, Per; Strömberg, Jessica; Bäckström, Torbjörn; Wang, Mingde (2003). "Allopregnanolone-stimulated GABA-mediated chloride ion flux is inhibited by 3β-hydroxy-5α-pregnan-20-one (isoallopregnanolone)". Brain Research. 982 (1): 45–53. doi:10.1016/S0006-8993(03)02939-1. ISSN 0006-8993.
- Abraham Weizman (1 February 2008). Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment. Springer Science & Business Media. pp. 8–9. ISBN 978-1-4020-6854-6.