Benzos What roles do the GABA subunits have in our bodily chemistry?

Amer2560 · Jan 2, 2021

I'm aware that different benzos target different GABA receptor subunits (im pretty sure?), and because of this they have different albeit similar effects. My question is how do each of the subunits effects differ compared to one and other. For example, what subjective/biological effects does a drug that targets the alpha-subunit specifically differ in subjective effect from a drug that targets beta subunits or messes with positive and negative ion channels (or whatever... I'm not particularly well versed in this stuff). So I suppose what I'm trying to get at is what roles do the different GABA subunits have on our brains and bodies?

Furthermore, how do Z-drugs and gabapentinoids differ in MOA to classic benzos?

fugme · Jan 2, 2021

AFAIK Z-drugs specifically target GABA A1 subunits which is largely responsible for the hypnotic effects. Some of them like zolpidem are more selective than others. There is a thread somewhere on bluelight with subunits explained and matched with benzos. Gabapentinoids act on VDCC, but don't agonize GABA receptors themselves.

4meSM · Jan 2, 2021

This is a pretty technical and complex question. I don't think it's possible to answer all of that in one post (maybe someone will prove me wrong).

Best I can do right now is provide some sources:

Structure, Function, and Modulation of GABAA Receptors

The GABA[A] receptors are the major inhibitory neurotransmitter receptors in mammalian brain. Each isoform consists of five homologous or identical subunits surrounding a central chloride ion-selective channel gated by GABA. How many isoforms of the ...

www.ncbi.nlm.nih.gov

A novel GABAA receptor pharmacology: drugs interacting with the α+β− interface

GABA[A] receptors are ligand-gated chloride channels composed of five subunits that can belong to different subunit classes. The existence of 19 different subunits gives rise to a multiplicity of GABA[A] receptor subtypes with distinct subunit composition; ...

www.ncbi.nlm.nih.gov

Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What?

Atomic resolution structures of cys-loop receptors, including one of a γ-aminobutyric acid type A receptor (GABAA receptor) subtype, allow amazing insights into the structural features and conformational changes that these pentameric ligand-gated ion channels (pLGICs) display. Here we present a...

www.frontiersin.org