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Ki values of common benzodiazepines

http://www.bluelight.org/vb/threads...nity-Chart?p=11115618&viewfull=1#post11115618

Code: 
triazolam	   1.31 umol
alprazolam	   1.38 umol
clonazepam	   1.43 umol
flunitrazepam	   1.60 umol
lorazepam  	   2.65 umol
loprazolam	   2.90 umol
lormetazepam	   3.58 umol
eszopiclone	   4.24 umol
estazolam  	   4.73 umol
bromazepam	  14.61 umol
quazepam	  17.06 umol
zaleplon	  19.65 umol
zopiclone	  21.22 umol
nitrazepam	  30.48 umol
diazepam	  32.67 umol
medazepam	  33.23 umol
nordazepam	  33.25 umol
clorazepate	  41.27 umol
prazepam	  41.56 umol
flurazepam	  47.08 umol
halazepam	  51.03 umol
ketazolam	  53.69 umol
clobazam	  59.90 umol
zolpidem	  59.90 umol
temazepam	  63.90 umol
oxazepam	  67.00 umol
chlordiazepoxide  75.00 umol

I suppose it's affinity to GABA-A receptors, no source, no detailed information unfortunately. I'm pretty sure I had found it somewhere on Bluelight and saved in a .txt file years ago, later I re-posted it after finding it on my flash drive by accident.

This is the original post I copied the values from:
http://www.bluelight.org/vb/threads...ween-Benzo-s?p=9485695&viewfull=1#post9485695
 
What can one really say from this data, that you don't really need the subunit affinities and efficacies for?

For example temazepam is listed as low affinity here, but it has a high gamma2 affinity and high physical dependency risk I think.

If that list on the other forum seems sketchy: it looks retyped cause it has typos so maybe a decimal point is missing?

Ki values shouldn't be cross-checked since they depend on the study and method, and what is measured should definitely never be omitted! But then again they should be consistent when comparing them relatively.
If it wasn't for that, someone shouldve definitely built a table for all opioids and gabaergics, that would be so informative.... :D

Please don't tell me some researchers are sitting on that treasure trove just like synthesis databases are not so publicly available afaik?
 
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I wouldn't be surprised if corporate/government enterprises know but they don't want to tell anyone else. Benzos are kind of a scandal.
 
^I'm a little confused by the post. Why would it be a scandel to characterize the pharmacology of benzodiazepines. Many members of that class are approved medications.

To the OP, if you want to find these values then you are going to have to dig through the medicinal chemistry literature. It is very difficult to compile these values because BZ receptor pharmacology depends on the underlying subunit composition of the GABA-A channel. The BZ site is formed at the interface of alpha and gamma subunits, so the structure of the BZ binding site depends on the subunits that happen to be present in the channel. So to study the affinity, you have to express many different subunit mixtures in cultured cells, and you end up with several Ki values for each drug.

An alternative has been to homogenize tissue and measure average affinity for all BZ binding sites that happen to be expressed in a particular brain region. However, that ki value is not necessarily relevant to other brain regions, let alone another species (because the subunit composition of GABA-A channels varies accross regions and species).
 
So, umol is the same as Ki ? I had seen that table, but was not aware it was the same.

serotonin2A, that is a very good point.
 
Kdem said:
So, umol is the same as Ki ? I had seen that table, but was not aware it was the same.

serotonin2A, that is a very good point.
Click to expand...
Ki is the ligand concentration that produces 50% occupation of a binding site -- as a concentration, it has to have some unit of measurement. Umol is the unit of measurement (ie, micromoles/L, usually abbreviated uM).
 
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'An alternative has been to homogenize tissue and measure average affinity for all BZ binding sites that happen to be expressed in a particular brain region. However, that ki value is not necessarily relevant to other brain regions, let alone another species (because the subunit composition of GABA-A channels varies accross regions and species).'

Another good point. Ki values depend on benzo/receptor/part of the brain.
So, Ki values don't mean that much except as a very crude indication ?
 
Anybody else notice that this table almost predicts abuse liability to a T? Surprise surprise, Xanax, Kpins, and Halcion are the most abused benzos.

How would one explain Temazepam's low affinity? It's also known to be a euphoriant
 
Kdem said:
So, Ki values don't mean that much except as a very crude indication ?
Click to expand...

No, I would say in general that couldn't be further from the truth. Ki is an excellent measure of ligand-receptor affinity. The problem here is that there isn't one single homogeneous population of benzodiazepine receptors, so one single Ki value is not sufficient to define benzodiazepine binding affinity.

At one time, pharmacologists tried to address these complexities by defining multiple BZ receptor subtypes (type I and type II, as defined below). But those attempts failed once it was recognized that each "subtype" was actually heterogeneous. Ultimately, it is necessary to define affinity based on a homogeneous population of binding sites.


http://www.ncbi.nlm.nih.gov/pubmed/11440203

"The subunit make-up of a receptor, particularly its alpha-subunit content, determines its pharmacological characteristics. Thus, receptors that include an alpha1 subunit have a benzodiazepine (BZ) type I (BZ) pharmacology and bind zolpidem and CL218,872 with high affinity, whilst receptors with alpha2, alpha3 or alpha5 subunits have a BZ type II (BZ[II]) pharmacology and bind these drugs with low affinity. In contrast to receptors that contain alpha4 and alpha6 subunits, which are diazepam-insensitive, both BZ(I) and -(II) bind diazepam and other benzodiazepines."
 
Does anyone have an actual source for the table mentioned in #2 ?

The Ki of nitrazepam seems a bit off.

Clorazepate itself is not supposed to be active, so ?
 
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^ Memantine correctly said the table says something about potency but not effects, it doesn't only say nothing about the effects like sedation vs. anxiolysis vs. hypnotic effect but also physical dependency and abuse liability. Posts 3 and 4 had that info.

I don't think the table predicts abuse liability that precisely, it only does partially because potency coincides a bit with some of the tendencies for heavy effects.
 
Great list - I think Brotizolam has the highest affinity of them all with 50-80ug active in man.
 
Hmm Fluorodeschlorobrotizolam would probably be in the 15-20ug range then.
 
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