Benzodiazepines Affinity Chart

[Hammilton]

I'll look into it starting today.

 

[LabRatNW]

According to wiki...

Xanax and Klonopin are roughly equivalent. There's NO WAY that's accurate. (Any pharmacist will tell you that.)

Did anyone notice a couple of trends in Benzo's function based on size and polarity?

I did, and as not to spoil it for anyone else, I have the observation below, in white.
More polar groups and larger size seem to lend themselves to the hypnotic camp; smaller, nonpolar ones tend to be more anxiolytic.

 

[Yopreacher]

Xanax and Klonopin are roughly equivalent. There's NO WAY that's accurate. (Any pharmacist will tell you that.)

Did anyone notice a couple of trends in Benzo's function based on size and polarity?

I did, and as not to spoil it for anyone else, I have the observation below, in white.
More polar groups and larger size seem to lend themselves to the hypnotic camp; smaller, nonpolar ones tend to be more anxiolytic.

Its the equivalence when calculating doses to withdraw mainly using diazepam, the wiki forgets to mention this rather important fact. And many users seem to believe the equivalence tables can be used when calculating potency of subjective effects between different benzodiazepines, this will at best give an approximation.

It would be great if someone made an extended equivalence table where the relative potency was calculated for hypnotic, anxiolytic and anticonvulsant effect.

 

[adder]

I don't know if this was resolved in any way. I found this table in my printed materials:

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 know a similar table (if not having all of these compared) was posted somewhere on Bluelight.

 

[Solipsis]

Great, thank you. Do we need to be concerned by benzo receptor subtypes much, and how is the above list measured?
I mean, it's not just a 2-dimensional model is it?

 

[adder]

It's a general list. I wish I had access to some paper with extensive numbers for al these substances fod different sub-units of BZD receptors. Such a list would tell which BZD is the best for anxiety or insomnia etc.

 

[Solipsis]

Best I can find is these classifications, but alass no numbers. Source is given though, maybe it is in that book...

We all know that benzos work by increasing the efficiency of a natural brain chemical, GABA, to decrease the excitability of neurons. This reduces the communication between neurons and therefore has a calming effect on many of the functions of the brain.

The GABA(A) receptor complex has many different subunits, which in turn have isoforms or otherwise known as subtypes (α1-6, β1-4, γ1-3, δ, ε, θ, and ρ1-2). Different benzodiazepines (BZD) have different affinities for GABA(A) receptors made up of different collection of subunits, and this means that their pharmacological profile varies with subtype selectivity. Only three of the subunits (α, β, and γ) are benzodiazepine sensitive. The α (alpha) subunit has 6 subtypes, but only α1, α2, α3, and α5 are BZD sensitive. The β (beta) subunit has 4 subtypes, but only the β3 subtype is BZD sensitive. The γ (gamma) subunit has 3 subtypes, but only the γ2 subtype is BZD sensitive.

Subunits from only one class (α) or two classes (α and β) can form functional GABA receptors under experimental conditions, but subunits from three classes (α, β, and γ) are needed for full receptor function. These three subunits also compose most of the GABA(A) receptors in the mammalian brain.


The Alpha (α) subunit

The most important subunit is the "alpha" (α) and its subtypes isoforms (α1,2,3,and 5). The alpha subunit is responsible for mediating most of the effects of the benzos. All benzos bind to this subunit but they also all have different affinitie levels to the different subtypes.

α1 subtype: Sedation, respiratory depression, sleep, ataxia, motor-impairment, amnesia, anti-convulsive, and reinforcing behavior.

α2 subtype: Anxiolysis, disinhibition

α3 subtype: Anxiolysis, anti-convulsive, muscle relaxation

α5 subtype: Learning and memory, amnesia, minor sedation

α3 & α5 subtype: Sensorimotor information processing

The Beta (β) and Gamma (γ) subunits

γ2 subtype: Physical dependence, respiratory depression

β3 subtype: Anti-convulsive, minor sedation, muscle relaxation, various other reactions related to respiration. This receptor subtype is a barbiturate receptor.

Benzos affinity to the GABA(A) receptors

High α1 affinity: midazolam, triazolam, flunitrazepam, temazepam, lormetazepam, nitrazepam, brotizolam, nimetazepam, loprazolam, and flutoprazepam.

Low to Moderate α1 affinity: wide range of 1,4 benzodiazepines including diazepam, estazolam, flurazepam, oxazepam, lorazepam, alprazolam, bromazepam, camazepam, quazepam (highly selective affinity), clonazepam, medazepam, nordazepam, chlordiazepoxide (very weak affinity), clorazepate, and most other benzo as all benzos are α1 agonists with varying degrees of affinity levels. Also included here are the nonbenzodiazepine "z-drugs" such as zolpidem, zaleplon, zopiclone, and eszopiclone which are all highly selective of the α1 subtype receptor but with only weak to moderate affinity.

High α2 affinity: diazepam, clonazepam, bromazepam, lorazepam, alprazolam, camazepam, nitrazepam, loprazolam, lormetazepam, and flutoprazepam.

Moderate α2 affinity: oxazepam, prazepam, phenazepam, temazepam, flunitrazepam, halazepam, midazolam, and other less commonly known benzos.

Weak α2 affinity: triazolam, chlordiazepoxide (stronger affinity for α3), brotizolam, quazepam, tetrazepam (stronger affinity for α3), and a few others.

High α3 affinity: diazepam, clonazepam, temazepam, lorazepam, tetrazepam, flunitrazepam, nimetazepam, phenazepam, and bromazepam.

Moderate α3 affinity: alprazolam, adinazolam, estazolam, chlordiazepoxide, clorazepate, and flurazepam.

High γ2 affinity (these benzos are the most physically addictive): temazepam, brotizolam, triazolam, alprazolam, lorazepam, loprazolam, midazolam, flunitrazepam, clonazepam, lormetazepam, flutoprazepam, nitrazepam, nimetazepam, and estazolam

Low to moderate γ2 affinity: diazepam, chlordiazepoxide, oxazepam, and most other benzos.

High β3 affinity: mostly the hypnotics (nitrazepam, temazepam, triazolam, etc)

Low to moderate β3 affinity: diazepam, alprazolam, most other benzos.


Source of all this info is this book which I purchased. It has A LOT of more useful info. It's worth its price.

http://www.bluelight.ru/vb/threads/550567-The-GABA(A)-Receptor-Complex-and-Benzodiazepines
http://www.ingentaconnect.com/conte...a6f3b6b4656236b675f4f6d62222c227e372530332976

 

[Temeraroius]

Great, thank you. Do we need to be concerned by benzo receptor subtypes much, and how is the above list measured?
I mean, it's not just a 2-dimensional model is it?

Benzos all bind to GABAa (ionotropic) selectively, GHB is the GABAb (metabatropic) agonist. They are thought to bind at the junction of the alpha and gamma subunits. In addition, benzos themselves do not open the Cl- channel but rather increase the GABAa affinity for GABA - the extent to which a benzo does this could be dependent upon its more than simply its affinity for the ligand binding domain, but it also might not be....

EDIT: oops, just saw the above post with all this information... but regardless, this mechanism of action is why all 3 subunits are necessary as GABA binding site on GABAa is between alpha and beta while the benzo site is between alpha and gamma.

 

[Non Nobis Solum]

I love this thread.

 

[Jabberwocky]

are there any subunits within the GABA system that are associated with euphoria? i know that temazepam has a listed side effect as euphoria in a low percentage of the population - is this modulated in correlation to specific binding in subsets?

 

[Captain.Heroin]

I don't know if this was resolved in any way. I found this table in my printed materials:

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 know a similar table (if not having all of these compared) was posted somewhere on Bluelight.

So I'm assuming it's pointless to take alprazolam, traizolam type high-affinity benzos when you're already on the lower potency ones?
It should be noted temazepam is the most toxic, oral BA is close to 100% and also "high addictiveness" compared to others. Odd.

I am also assuming if you're taking relatively low dosages of alprazolam/traizolam together (i.e. 1mg alpraz, 1mg triazolam oral or 0.5mg nasal) the almost similar #'s and relatively low dosages would mean you probably are going to feel both synergize.

Why did I feel flurazepam + alprazolam combos years ago so thoroughly, then? Relatively low dosages?