Pregnanolone, also known as eltanolone, is an endogenous inhibitory neurosteroid which is produced in the body from progesterone.
Biological activity
Pregnanolone is a positive allosteric modulator of the
GABAA receptor,
as well as a negative allosteric modulator of the
glycine receptor.
Biological function
Pregnanolone has
sedative,
anxiolytic,
anesthetic, and
anticonvulsant effects.
During
pregnancy, pregnanolone and
allopregnanolone are involved in
sedation and
anesthesia of the
fetus.
Biochemistry
Pregnanolone is synthesized from
progesterone via the
5β-reductase and 3α-hydroxysteroid dehydrogenase, with 5β-dihydroprogesterone occurring as a metabolic intermediate. The elimination half-life of pregnanolone is between 0.9 and 3.5 hours.
Chemistry
Pregnanolone, also known as 3α,5β-tetrahydroprogesterone (3α,5β-THP) or as 5β-pregnan-3α-ol-20-one, is a
natural product pregnane steroid and a derivative of
progesterone. Related compounds include
allopregnanolone (3α,5α-THP; brexanolone),
epipregnanolone (3β,5β-THP),
hydroxydione,
isopregnanolone (3β,5α-THP), and
renanolone.
History
Pregnanolone was first isolated from the
urine of pregnant women in 1937.
Its anesthetic properties were first demonstrated in animals in 1957.
Research
Pregnanolone was investigated for clinical use as a general anesthetic under the name
eltanolone (), but produced unwanted
such as
on occasion, and for this reason, was never marketed.
