Agis-balboa and neurosteroids

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]

Agis-balboa and neurosteroids

agis-balboa and neurosteroids

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