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Re: NDA Submitted for Postpartum Depression Drug

Posted by SLS on April 25, 2018, at 5:38:57

In reply to Re: NDA Submitted for Postpartum Depression Drug, posted by sigismund on April 24, 2018, at 23:58:36

> >Brexanolone is a proprietary allosteric modulator of both synaptic and extra synaptic GABAA receptors.
>
> Can anyone put this in more simple terms?

No.

:-)

Summary:
Brexanolone is a synthetic form of the naturally-occurring hormone, allogregnanolone, the levels of which become very high during pregnancy. It is given intravenously (IV). It is likely to improve post-partum depression and anxiety in women only when levels drop after childbirth.


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Allosteric = Changes the shape of (a protein).
Modulator = Adjust the activity of
Synapse (synaptic) = Where one neuron transfers a message to another at the terminal-dendrite junction
Extra synaptic = Where one neuron adjusts the activity of another at a site other than the synapse.
GABA = Gaba amino butyric acid; the most numerous inhibitory neurotransmitter. It puts the "brakes" on the excitatory neurons throughout the brain.
GABA-A = GABA receptor responsible for reducing anxiety and promoting sleep. It adjusts the actiivity of other types of neurons.

Brexanolone is an intravenous form of the naturally occurring hormone, allopregnanolone. Allopregnanolone, a neurosteroid, is a product of progesterone - one of the two primary hormones involved in female reproductive function. Normally, it regulates and supports GABA-A receptors. Immediately upon childbirth, levels of progesterone and allopregnanolone drop precipitously, which prevents GABA neurons from functioning nominally. As a result, depression and anxiety emerges in many women. I'm guessing that during pregnancy, there is tolerance to higher levels of allopregnanolone - maybe through reduced GABA receptor numbers. So, dropping allopregnalol too fast may look like a sort of withdrawal, perhaps similar to benzodiazepine or SSRI withdrawal.


- Scott


Some see things as they are and ask why.
I dream of things that never were and ask why not.

- George Bernard Shaw

 

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