Does tolerance to the more sedating benzodiazepine develop faster than 'non sedating'

[Dret]

benzos like alprazolam or clonazepam. In the sense, does tolerance to benzos that act on the alpha 1 subunit occur faster than on those that act primarily on the alpha 2 and 3 subunit ?

 

[Cotcha Yankinov]

My text has said that tolerance to the sedative effects (primarily mediated via a1) develops faster, while tolerance to the amnestic, anxiolytic and muscle relaxant properties develop much slower.

 

[Solipsis]

Going on what Cotcha has said before (I think), maybe it's that benzo like diazepam are too broad-spectrum / unselective to do that kind of thing, since inappropriate activity at one receptor may get partially evened out by activity at others? Not quite the homeostatic principle, but still....

I'm not sure anything about that post really answers the question directly though (no offense)... what comes to mind is that perhaps the reason is that alpha1 subunit containing types are a whole other class? Gamma 1 vs gamma 2, with different areas of expression?

 

[Kdem]

Solipsis,

http://www.bluelight.org/vb/threads/550567-The-GABA(A)-Receptor-Complex-and-Benzodiazepines

https://www.ncbi.nlm.nih.gov/pubmed/9014158

´Native GABAA receptors containing different gamma-subunit variants were distinguished immunobiochemically with antisera selectively recognizing the gamma 1-, gamma 2- and gamma 3-subunits. While GABAA receptors containing the gamma 2-subunits were confirmed to be rather ubiquitous in the adult brain, receptors characterized by the gamma 1- or gamma 3-subunit were of low abundance, as shown by immunoprecipitation.´

So they bind (mostly) to gamma2 ?

 

[Solipsis]

What is 'they' ? Different benzos have different affinities, some are listed in that bluelight thread. What I meant is that yes there seem to be different combinations of subtypes together but some combinations are found especially often I think, and yes they are found relatively unevenly in different parts of the CNS. The whole gamma subunit thing is just part of that it seems, so hopefully it is not misleading and not an answer in itself. My point was just to add to what cotcha said, to perhaps help explain why the tolerance behavior may be so differently between alpha1 and other alpha subunit containing GABAR complexes: that alpha1 containing ones are found in different circumstances, so there are a lot of other differences. I thought that might make it more understandable.

But I'm still just venturing a guess, g0to, I am not sure.