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Comment by 01100011 | Hacker News Reader

https://en.wikipedia.org/wiki/Zuranolone

"An orally active inhibitory pregnane neurosteroid, zuranolone acts as a positive allosteric modulator of the GABAA receptor."

Interesting. I was expecting another SSRI or something similar.

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The inhibitory effect seems a bit surprising.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139029/#:~:tex....

https://en.wikipedia.org/wiki/Pregnanolone#Biological_functi...

“positive allosteric modulator of the GABAA receptor”, isn’t that a benzodiazepine?

edit: nevermind i guess drugs are classified by their chemistry rather than their effects

Drugs can be variously classified by their chemistry and/or by their effects. It's worth noting that GABA-A receptors have multiple allosteric sites, and different chemical classes of PAMs (positive allosteric modulators) may have differences in effects. (There certainly seems to be substantial overlap in effects, of course.)

Technically it's a Z-drug (like Zolpidem/Ambien) which are non-benzodiazapine positive allosteric modulators of GABA_A

However, since it's a neurosteroid most will probably not think of it as such. (It's name does begin with Z though... And end in -one like a steroid).

Anyways, it's licensed for 2 weeks only, side effects are drowsiness, sleepiness and cognitive impairment. You mustn't drive within 12 hours of a dose.

It's best effects are where the depression is associated with insomnia and anxiety.

It was compared to placebo not Alprazolam (Xanax) which has some antidepressant activity.

Benzos directly hammer on GABA receptors while pregnanes use G coupled progesterone receptors to transduct signals to the GABA system.

Benzos attach to the benzodiazepine subunits on GABA receptors, and according to this paper[1], neurosteroids like this one also attach to similar subunits on GABA receptors[2]. Both act as positive allosteric modulators when activating their respective subunits on GABA receptors.

This cited paper[3] also tested similar neurosteroids in progesterone receptor knockout mice and still found anxiolytic effects.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139029

[2] See Figure 3A in [1]

[3] https://pubmed.ncbi.nlm.nih.gov/15617723

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