Allopregnanolone, is a neurosteroid that acts on the brain.
As a medication, it is sold under the brand name Zulresso and used to treat postpartum depression.
It is used by injection into a vein over a 60-hour period under medical supervision.
Schedule IV drug.
Protein binding greater than 99%.
Metabolism mechanisms. Non-CYP450
Elimination half-life 9 hours.
Excretion Feces: 47% and Urine: 42%
Side effects may include sleepiness, dry mouth, and loss of consciousness.
It is a neurosteroid.
It acts as a positive allosteric modulator of the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).
It is used to treat postpartum depression in women.
It possesses effects, including: antidepressant, anxiolytic, stress-reducing, rewarding, prosocial, antiaggressive, prosexual, sedative, pro-sleep, cognitive, memory-impairment, analgesic,anesthetic, anticonvulsant, neuroprotective, and neurogenic effects.
Fluctuations in the levels of allopregnanolone and the other neurosteroids have an important role in the pathophysiology of mood, anxiety, premenstrual syndrome, catamenial epilepsy, and various other neuropsychiatric conditions.
Increased levels of allopregnanolone can produce paradoxical effects, including negative mood, anxiety, irritability, and aggression.
Allopregnanolone possesses biphasic, U-shaped actions at the GABAA receptor.
Moderate level increases of allopregnanolon, which are approximately equivalent to luteal phase levels, inhibit the activity of the GABAA receptor, while lower and higher concentration increases stimulate it.
The administration of low doses of micronized progesterone, which elevates allopregnanolone levels,has been found to have negative effects on mood, while higher doses have a neutral effect.
During pregnancy, allopregnanolone and pregnanolone are involved in sedation and anesthesia of the fetus.
Allopregnanolone is an endogenous inhibitory pregnane neurosteroid.
Allopregnanolone is made from progesterone, and is a positive modulator of the action of γ-aminobutyric acid (GABA) at GABAA receptor.
It has effects similar to those of other positive modulators of the GABA action at GABAA receptor such as the benzodiazepines, including anxiolytic, sedative, and anticonvulsant activity.
Allopregnanolone neurophysiologically fine-tunes GABAA receptors and is an agonists at GABAA receptor.
It is, unlike progesterone, inactive at the classical nuclear progesterone receptor (PR), however it can be intracellularly oxidized into 5α-dihydroprogesterone, which does act as an agonist of the PR,.
For this reason, allopregnanolone can produce PR-mediated progestogenic effects.
The biosynthesis of allopregnanolone in the brain is by cortical and hippocampus pyramidal neurons and pyramidal-like neurons of the basolateral amygdala.
Oral progesterone, elevates allopregnanolone levels in the body with good dose-to-serum level correlations.