Neuroactive Steroids (NAS)

Not all neuroactive steroids are created equal from this chart and abstract below. That may be important when comparing Sage Therapeutics SAGE-217 to Marinus Pharmaceuticals drug Ganaxolone for patients with Postpartum Depression. First let's look at a chart that compares oral SAGE-217 to IV SAGE-547 and IV Ganaxolone for synaptic and extrasynaptic activity of each.

 

SAGE-217 shows much more activity in both synaptic and extrasynaptic activity over a given time period.  Below is another illustration that not all is created equal when considering tonic current. https://www.ncbi.nlm.nih.gov/pubmed/27743930. Here is a paragraph from that abstract.

A sustained increase in tonic current was observed following exposure to ALLO, or SGE-516 and was prevented by inhibiting PKC with GF 109203X. No increase in tonic current was observed with exposure to ganaxolone. In agreement with the observations of an increased tonic current, the NASs ALLO and SGE-516 increased the phosphorylation and surface expression of the β3 subunit-containing GABAARs. Our studies demonstrate that neuroactive steroids have differential abilities to induce sustained increases in the efficacy of tonic inhibition by promoting GABAAR phosphorylation and membrane trafficking dependent on PKC activity.

Thank you for reading.