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 depression. It is used by injection into a vein over a 60-hour period under medical supervision.Side effects of brexanolone may include sedation, sleepiness, dry mouth, hot flashes, and loss of consciousness. It is a neurosteroid and acts as a positive allosteric modulator of the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).Brexanolone was approved for medical use in the United States in 2019. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. The long administration time, as well as the cost for a one-time treatment, have raised concerns about accessibility for many women. Medical uses
Brexanolone is used to treat postpartum depression in adult women. Side effects
Side effects of brexanolone include sedation (13–21%), dry mouth (3–11%), loss of consciousness (3–5%), and flushing (2–5%). It can also produce euphoria to a degree similar to that of alprazolam (3–13% at infusion doses of 90–270 μg over a one-hour period). Biological function
Allopregnanolone possesses a wide variety of effects, including, in no particular order, antidepressant, anxiolytic, stress-reducing, rewarding, prosocial, antiaggressive, prosexual, sedative, pro-sleep, cognitive, memory-impairment, analgesic, anesthetic, anticonvulsant, neuroprotective, and neurogenic effects.
Each mL of brexanolone solution contains 5 mg allopregnanolone, 250 mg sulfobutyl ether β-cyclodextrin, 0.265 mg citric acid monohydrate, 2.57 mg sodium citrate dihydrate, and water for injection. The solution is hypertonic and must be diluted to a target concentration of 1 mg/mL with sterile water and sodium chloride prior to administration. Five infusion bags are generally required for the full infusion. More than five infusion bags are necessary for patients weighing more than 90 kg (200 lbs). Research
Brexanolone was under development as an intravenously administered medication for the treatment of major depressive disorder, super-refractory status epilepticus, and essential tremor, but development for these indications was discontinued.Exogenous progesterone, such as oral progesterone, elevates allopregnanolone levels in the body with good dose-to-serum level correlations. Due to this, it has been suggested that oral progesterone could be described as a prodrug of sorts for allopregnanolone. As a result, there has been some interest in using oral progesterone to treat catamenial epilepsy, as well as other menstrual cycle-related and neurosteroid-associated conditions. In addition to oral progesterone, oral pregnenolone has also been found to act as a prodrug of allopregnanolone, though also of pregnenolone sulfate. References
Further reading
External links
"Brexanolone". Drug Information Portal. U.S. National Library of Medicine.