Allopregnanolone

Allopregnanolone, also known as brexanolone, is a medication and a naturally produced steroid 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. Allopregnanolone, also known as brexanolone, is a medication and a naturally produced steroid 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. Side effects of brexanolone may include sleepiness, dry mouth, 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 with commercial sales expected to begin in June 2019. The long administration time, as well as the cost of US$34,000, have raised concerns about accessibility for many women. Brexanolone is used to treat postpartum depression in women. Side effects may include sleepiness, dry mouth, and loss of consciousness. 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. Fluctuations in the levels of allopregnanolone and the other neurosteroids seem to play 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. This appears to be because allopregnanolone possesses biphasic, U-shaped actions at the GABAA receptor – moderate level increases (in the range of 1.5–2 nM/L total allopregnanolone, which are approximately equivalent to luteal phase levels) inhibit the activity of the receptor, while lower and higher concentration increases stimulate it. This seems to be a common effect of many GABAA receptor positive allosteric modulators. In accordance, acute administration of low doses of micronized progesterone (which reliably 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. It is an endogenous inhibitory pregnane neurosteroid. It is made from progesterone, and is a positive allosteric modulator of the action of γ-aminobutyric acid (GABA) at GABAA receptor. Allopregnanolone has effects similar to those of other positive allosteric modulators of the GABA action at GABAA receptor such as the benzodiazepines, including anxiolytic, sedative, and anticonvulsant activity. Endogenously produced allopregnanolone exerts a neurophysiological role by fine-tuning of GABAA receptor and modulating the action of several positive allosteric modulators and agonists at GABAA receptor.