Chemistry:Isopregnanolone

From HandWiki
Isopregnanolone
Isopregnanolone.svg
Names
IUPAC name
3β-Hydroxy-5α-pregnan-20-one
Systematic IUPAC name
1-[(1S,3aS,3bR,5aS,7S,9aS,9bS,11aS)-7-Hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-1-yl]ethan-1-one
Other names
Isoallopregnanolone; Epiallopregnanolone; Sepranolone; 3β,5α-Tetrahydroprogesterone; 3β,5α-THP
Identifiers
3D model (JSmol)
ChemSpider
UNII
Properties
C21H34O2
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).
Infobox references
Tracking categories (test):

Isopregnanolone, also known as isoallopregnanolone and epiallopregnanolone, as well as sepranolone (INN), and as 3β-hydroxy-5α-pregnan-20-one or 3β,5α-tetrahydroprogesterone (3β,5α-THP), is an endogenous neurosteroid and a natural 3β-epimer of allopregnanolone.[1][2] It has been reported to act as a subunit-selective negative allosteric modulator of the GABAA receptor,[2] and antagonizes in animals and humans some but not all of the GABAA receptor-mediated effects of allopregnanolone, such as anesthesia,[3] sedation,[4] and reduced saccadic eye movements,[4] but not learning impairment.[2] 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.[1][5]

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)[6] and can be reversibly metabolized into allopregnanolone by the enzyme 3α-hydroxysteroid dehydrogenase.[1][2] Levels of isopregnanolone, progesterone, and allopregnanolone are highly correlated across the menstrual cycle and throughout pregnancy.[1] The concentrations of isopregnanolone are significantly less than those of progesterone and allopregnanolone; about half of those of allopregnanolone, to be precise.[6] Isopregnanolone has a relatively long serum elimination half-life of 14 hours in humans.[1]

Isopregnanolone (developmental code name UC-1010) is under development for the treatment of premenstrual dysphoric disorder.[7][8] As of 2017, it is in phase II clinical trials for this indication.[7][8]

Chemistry

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women". Psychopharmacology 203 (1): 85–98. 2009. doi:10.1007/s00213-008-1372-8. PMID 18949461. http://umu.diva-portal.org/smash/get/diva2:455421/FULLTEXT02. 
  2. ↑ 2.0 2.1 2.2 2.3 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
  3. ↑ "Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats". Eur. J. Pharmacol. 512 (1): 15–21. 2005. doi:10.1016/j.ejphar.2005.01.049. PMID 15814085. 
  4. ↑ 4.0 4.1 "Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans". Psychoneuroendocrinology 52: 22–31. 2015. doi:10.1016/j.psyneuen.2014.10.025. PMID 25459890. 
  5. ↑ 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. PMID 12915239. 
  6. ↑ 6.0 6.1 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. https://books.google.com/books?id=uABKkFdPjhkC&pg=PA8. 
  7. ↑ 7.0 7.1 "Sepranolone - Asarina Pharma - AdisInsight". http://adisinsight.springer.com/drugs/800036513. 
  8. ↑ 8.0 8.1 "Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial". Psychoneuroendocrinology 80: 46–55. 2017. doi:10.1016/j.psyneuen.2017.02.031. PMID 28319848. 

External links

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See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators

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