What is allopregnanolone used for?

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.

What is 5a DHP?

Infobox references. 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 isopregnanolone from progesterone.

Is allopregnanolone the same as pregnenolone?

Pregnenolone is lipophilic and readily crosses the blood brain barrier. We have previously found that pregnenolone is preferentially metabolized to allopregnanolone, rather than other compounds such as cortisol or DHEA (43, 44); however these metabolites were also assayed.

How do Neurosteroids work?

Neurosteroids are broad-spectrum anticonvulsant agents. They protect against seizures induced in animals by GABA-A receptor antagonists, pilocarpine-induced limbic seizures, and kindled seizures (Belleli et al., 1989; Kokate et al., 1994; Frye, 1995; Wieland et al., 1995; Reddy et al., 2004).

What causes low allopregnanolone?

Reduced levels of allopregnanolone are found to be associated with major depression, anxiety disorders, premenstrual dysphoric disorder, and Alzheimer’s disease.

Does progesterone turn into allopregnanolone?

Progesterone is also locally synthesized by the nervous system and qualifies, therefore, as a neurosteroid. In addition, the nervous system has the capacity to bio-convert progesterone into its active metabolite allopregnanolone.

Is progesterone converted to allopregnanolone?

Progesterone is converted to allopregnanolone in a two-step process by the enzymes 5α-reductase, which converts progesterone to 5α-dihydroprogesterone (5α-DHP), and 3α-hydroxysteroid-dehydrogenase (3α-HSD), which converts 5α-DHP to allopregnanolone (King, 2013).

Are neurosteroids important?

Function. Some major known biological functions of neurosteroids include modulation of neural plasticity, learning and memory processes, behavior, and seizure susceptibility, as well as responses to stress, anxiety, and depression.

Which of the following is neurosteroids?

Neurosteroids are synthesized in astrocytes, oligodendrocytes, Schwann cells, Purkinje cells, hippocampal neurons, and retinal amacrine and ganglion cells. Cholesterol is transported to glial mitochondria, where it is converted to pregnenolone.

How do you increase allopregnanolone?

Several antidepressants of the SSRI type have been shown to potently increase the levels of allopregnanolone in rodents and depressed humans. Paroxetine and fluoxetine increased the levels of allopregnanolone in rats and mice without affecting the levels of pregnenolone or progesterone (35).

Does finasteride affect neurosteroids?

Finasteride alters the concentrations of several neurosteroids, a term that refers to steroids that are locally synthesized in the brain or are metabolized in the brain from steroids produced within the gonads or adrenal glands.

Where are neurosteroids produced?

Similar to the adrenal glands, gonads, and placenta, vertebrate brains also produce various steroids, which are known as “neurosteroids.” Neurosteroids are mainly synthesized in the hippocampus, hypothalamus, and cerebellum; however, it has recently been discovered that in birds, the pineal gland, a photosensitive …