Nordazepam a unique benzo? GABA-A partial agonism vs positive allosteric modulation

[Memantine]

What is the difference in effect and dependence potential of nordazepam vs other benzo's?

 

[serotonin2A]

Nordiazepam binds to the same site as other benzodiazepines, but is a partial agonist.

http://onlinelibrary.wiley.com/doi/10.1111/j.2042-7158.1987.tb03404.x/abstract

 

[aced126]

How, in terms of binding, could the loss of the methyl group have a significant effect on the intrinsic activity of the compound? All I can think of is that due to a new H-bond donor in the molecule, that could facilitate a binding mode which only results in partial agonism.

 

[serotonin2A]

How, in terms of binding, could the loss of the methyl group have a significant effect on the intrinsic activity of the compound? All I can think of is that due to a new H-bond donor in the molecule, that could facilitate a binding mode which only results in partial agonism.

In the existing benzodiazepine pharmacophore, that part of the molecule is believed to interact with a H-bond donor in the binding site (even the partial agonists). But the efficacy difference could be something as simple as a change in the H-bond angle, a change in the angle/stregnth of a pi stacking interaction, or a difference in the number of water molecules excluded from the site.

 

[Kdem]

#1, The dependence potential may be lower, but I could be wrong about that.

 

[Cotcha Yankinov]

I think my textbook said something about how partial agonists possibly may not produce the same sort of long term benzo receptor changes that are seen with full agonists. I could be remembering wrong.

 

[Kdem]

#6,

I seem to remember having read something like that. But does anyone have a source ?