Isopregnanolone, also known as isoallopregnanolone and epiallopregnanolone, as well as sepranolone (), and as 3β-hydroxy-5α-pregnan-20-one or 3β,5α-tetrahydroprogesterone (3β,5α-THP), is an

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

neurosteroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was coin ...

and a

natural Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are p ...

3β-

epimer In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in each. Epimerization is ...

allopregnanolone Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum d ...

.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 It has been reported to act as a subunit-selective

negative allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds t ...

of the GABA_A receptor, and antagonizes in animals and humans some but not all of the GABA_A receptor-mediated effects of allopregnanolone, such as

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, and reduced

saccadic eye movement A saccade ( , French for ''jerk'') is a quick, simultaneous movement of both eyes between two or more phases of fixation in the same direction.Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishin ...

s, but not learning impairment. Isopregnanolone has no

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required fo ...

effects and appears to have no effect on the GABA_A receptor by itself; it selectively antagonizes allopregnanolone and does not affect the effects of other types of GABA_A receptor

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

s such as

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s or

barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as we ...

s. Isopregnanolone is synthesized from

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

in the body by the actions of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

5α-reductase 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...

and 3β-hydroxysteroid dehydrogenase (with

5α-dihydroprogesterone 5α-Dihydroprogesterone (5α-DHP, allopregnanedione, or 5α-pregnane-3,20-dione) is an endogenous progestogen and neurosteroid that is synthesized from progesterone. It is also an intermediate in the synthesis of allopregnanolone and isopre ...

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 The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

and throughout

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. 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 Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of 14 hours in humans. Isopregnanolone (developmental code name UC-1010) is under development for the treatment of

premenstrual dysphoric disorder Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms that cause significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptoms ...

. As of 2017, it is in phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s for this indication.

Chemistry

References

External links

Sepranolone - AdisInsight

Sepranolone - Asarina Pharma
{{GABA receptor modulators GABAA receptor negative allosteric modulators Neurosteroids Pregnanes

Chemistry

See also

References

External links