Isopregnanolone, also known as isoallopregnanolone and epiallopregnanolone, as well as sepranolone (), and as 3ò-hydroxy-5ñ-pregnan-20-one or 3ò,5ñ-tetrahydroprogesterone (3ò,5ñ-THP), is an endogenous neurosteroid and a natural 3ò-epimer of allopregnanolone. It has been reported to act as a subunit-selective negative allosteric modulator of the GABA<sub>A</sub> receptor, and antagonizes in animals and humans some but not all of the GABA<sub>A</sub> 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 GABA<sub>A</sub> receptor by itself; it selectively antagonizes allopregnanolone and does not affect the effects of other types of GABA<sub>A</sub> receptor positive allosteric modulators such as benzodiazepines or barbiturates.
Isopregnanolone is synthesized from progesterone in the body by the actions of the enzymes 5ñ-reductase and 3ò-hydroxysteroid dehydrogenase (with 5ñ-dihydroprogesterone as the intermediate in this two-step transformation) and can be reversibly metabolized into allopregnanolone by the enzyme 3ñ-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 elimination half-life of 14 hours in humans.
Isopregnanolone (developmental code name UC-1010) is under development for the treatment of premenstrual dysphoric disorder. As of 2017, it is in phase II clinical trials for this indication.