Neurosteroid synthesis

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]

Unlike benzodiazepines, etifoxine appears to produce its anxiolytic effects by activating β2 and β3 subunit containing channels of the GABA A receptor complex (a different binding site than benzodiazepines), and by stimulating the production of GABA(A) active neurosteroids that act in conjunction with etifoxine's direct effects. [9] This difference in binding means that etifoxine can be used alongside benzodiazepines to potentiate their effects without competing for binding sites; [10] however, it also means that the effects of etifoxine are not reversed by the benzodiazepine antagonist flumazenil . [11]

Description:   We provide consultation and services for the following: 1. Multiparameter cell phenotyping up to 11-color antibody combinations. 2. Analysis applications such as cell activation, proliferation, cell cycle/DNA content, apoptosis, surface marker expressions, intracellular expressions, quantification of internal, regulatory and structural proteins and quantification of reporter genes (GFP, DsRed, mCherry, etc). 3. High-speed cell sorting of live and biohazardous samples, single-cell deposition into 96-well plates. Core instruments include: MoFlo XDP sorter, FACSAria II sorter, FACSCanto analyzers.

Neurosteroid synthesis

neurosteroid synthesis

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