Neurosteroids gaba a receptor function

In the mid 1980s, the neuroactive steroids 3α,5α-tetrahydroprogesterone or allopregnanolone (3α,5α-THP) and 3α,5α- tetrahydrodeoxycorticosterone (3α,5α-THDOC) were shown to modulate neuronal excitability via their interaction with GABA A receptors. The steroids 3α,5α-THP and 3α,5α-THDOC were able to enhance the GABA-elicited Cl − current. [13] In addition, these steroids might enhance the binding of muscimol and benzodiazepines to GABA A receptors. [30] Structure- activity studies (SAR) showed that the 3alpha-OH group is essential for the anesthetic actions of these steroids, [31] they also have an optimally-placed hydrogen bond accepting group on the β face of the steroid at the C-17 position. The four steroid rings form a rigid framework for positioning these hydrogen groups in three-dimensional space. [32] Analogues 5 and 6 (Figure 10) are weak modulators of GABA A receptor function because the flexible side chains in these analogues do not have the conformations required for high biological activity. [33]

Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5α-androstane-3α,17β-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation.

I believe we're going to find that pregnenolone has amazingly more CNS benefits than estrogen. I asked Dr. James Flood, who is a researcher involved in testing the effects of pregnenolone on memory in mice, "What do you think about hormone replacement with pregnenolone in older age? Do you think it is appropriate?" And he said, "Of course." His feeling was that replacement would lead to more energy, and more positive outlook, and certainly an improvement in memory, but he is concerned about young people in their 20s who have relatively normal pregnenolone levels taking excessive amounts for many, many years, because he thinks that may down-regulate certain receptors in the brain. But I don't think any of us are recommending that young people take it continuously.

Neurosteroids gaba a receptor function

neurosteroids gaba a receptor function


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