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Most Potent Benzodiazepine?

kokaino

kokaino

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What's the most potent benzodiazepine that is approved for human use?

Is it triazolam or is it brotizolam?
 
I think you would do well to find & read the patents on them. I have seen them but forget the figures. They are in there (for rats, I admit). In spite of this, everyone reacts differently to a drug so it's not conclusive. To sum up - who knows?
 
^ as in the benzodiazepine antagonist flumazenil? Not what I think the OP was looking for.

I imagine somewhere out there someone has thought up some super-potent benzo analogues? Not something I'm familiar with, but I bet they're out there in the literature...

Phenazepam is up there.
 
Damn, I wonder how this passes as Advanced Drug Discussion material. Oh well, I am sure the ADD mods are busy multitasking elsewhere (horrible joke, sorry).
 
Potency doesn't make something inherently better. There are some highly potent members of the class but they all seem to have a steep dose/response curve.

Read the patents.
 
^ very true. to me the best benzodiazepines, subjectively, are the relatively weak (potency wise) bromazepam and diazepam (In that order).

Apostacious said:
Damn, I wonder how this passes as Advanced Drug Discussion material.
Click to expand...

also very true :|
 
The only reason I posted it was because someone claimed that alprazolam and triazolam are equipotent just because the outdated Ashton Manual said so.

I know very well potency doesn't make a drug better. Temazepam is my favorite benzo, and the favorite of many, but its not the most potent.

The Ashton Manual claims 0.5 mg alprazolam = 0.5 mg triazolam - whichi I don't agree with, as I think the Ashton Manual is outdated. It still has some great info in it and all, but her chart is way outdated.

It's 2011, we all know now that that is not true.


Correct?
 
kokaino-

I think you misunderstand what the Ashton Manual benzodiazepine equivalency tables are supposed to represent. They are dosage equivalency tables in terms of mitigating withdrawal symptoms. For example, let's say you take 1 gram of halcion/triazolam 3 times a day for 6 months and you wish to taper off with the aid of a drug that has a FAAAR longer half life, which Prof Ashton rightly advocates to be diazepam. Therefore, you would be transitioned over to 20 mg diazepam taken 3 times a day. The same protocol exists for alprazolam at 1mg 3 times a day. It has nothing to do with subjective effects (i.e., how high it gets you), but rather, what the correct dose of diazepam would be for the patient to transition over to. Obviously, transitioning to a too low of a dose would cause withdrawal symptoms for the patient, and transitioning to a too high of a dose would lengthen the dependence, since the patient is to then taper the dose by 10% every two weeks once the patient has fully transitioned over to diazepam and has stabilized.
 
What are we referring to this week when we say "potency"? I believe the medical literature and pharmacological literature will refer to 2 different things when using that word.

I'd be interested in finding out Ki values for benzos: not human dosages but receptor Ki values. Comparative.

Also, before a colonoscopy a few years ago, I was surprised to receive IV midazolam. Immediate onset for that. I think it was meant to put me under, but the nurse was not aware that I had enormous tolerance. I think I started coming on to the entire room (which is not always advisable prior to having a tube stuck through your rectum; possibly never).
 
It is a bit more complicated...........the typical "benzodiazapine receptor" is coupled to the GABA-A at the alpha-gamma subunit interface (and these can be uncoupled in theory and practice, or at least as far as i can recall). But simply put, based on the selectivity of a BZR ligand, you might have a compound that is technically "an ultra-potent" BZR ligand, but has little intrinsic activity. In other words, even if a ligand binds somewhere to the BZR with absurd affinity, it may not have a proportional result in (+) GABA-A modulation.

The point is, studies on the SAR/QSAR of benzos and BZR ligands are voluminous, and there are certainly compounds that are uniquely anxioselective and highly potent. The old consensus is that all + GABA-A mod benzos are (dose-dependent) anxiolytic/hypnotic/muscle relaxant, but in reality, there are selective benzos, and obviously, ligands such as some of the imidazopyridines which are actually rather selection in activity.

But more basically, yes, Halcion is the one of the most "potent benzos" one will run into in a clinical setting. It is also not widely prescribed due to a number of incidents involving paradoxical reactions, tricky pharmacokinetics and amnesia.........
 
^The ratio of α5 activity is too high, I suspect. Most of the '2 substituted benzodiazepines have the tendency to cause weird behaviour in humans. I think the fact that diazepam & alprazolam seem to be the most widely prescribed (low incidence of side-effects).

If someone is interested, it's possible to get the Ki for the six main binding sites of various from articles & produce a table of ratios. I did have one once, the '2 made a BIG difference.

The strongest benzodiazepine in production (I think) is zolazepam. It usually comes as an admixture with tiletamine for knocking out animals.
 
fencamfamine said:
The strongest benzodiazepine in production (I think) is zolazepam. It usually comes as an admixture with tiletamine for knocking out animals.
Click to expand...

I think maybe the mixture provides the strength and zolazepam is not so strong on it's own?

(unless it's a Lebron James type of thing where the best in the world still needs help)
 
Apostacious said:
kokaino-

I think you misunderstand what the Ashton Manual benzodiazepine equivalency tables are supposed to represent. They are dosage equivalency tables in terms of mitigating withdrawal symptoms. For example, let's say you take 1 gram of halcion/triazolam 3 times a day for 6 months and you wish to taper off with the aid of a drug that has a FAAAR longer half life, which Prof Ashton rightly advocates to be diazepam. Therefore, you would be transitioned over to 20 mg diazepam taken 3 times a day. The same protocol exists for alprazolam at 1mg 3 times a day. It has nothing to do with subjective effects (i.e., how high it gets you), but rather, what the correct dose of diazepam would be for the patient to transition over to. Obviously, transitioning to a too low of a dose would cause withdrawal symptoms for the patient, and transitioning to a too high of a dose would lengthen the dependence, since the patient is to then taper the dose by 10% every two weeks once the patient has fully transitioned over to diazepam and has stabilized.
Click to expand...

Dude...if you're taking 1 gram of triazolam a day, you are lucky to know that you're taking 1 gram of triazolam a day.
 
Lol im thinking 1mg is meant which makes sense more or less
 
Ahh!
Brotizolam, available as Lindormin in my country (Mexico) is more potent (slightly), it's half-life is also slightly longer than the triazolam, and is easier to get.
Other than those, you have Xanax (Alprazolam) and Rivotril (Clonazepam), Alprazolam is a little bit more potent but Clonazepam lasts much longer, and is very easy to get.
 
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