Names | |
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IUPAC name
3β-Hydroxy-5α-pregnan-20-one
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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 | |
ECHA InfoCard | 100.007.478 |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
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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).
|
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]
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 | |
ECHA InfoCard | 100.007.478 |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
| |
| |
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).
|
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]