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Rilmazafone & Avizafone

RedLeader

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Just read up on rilmazafone and avizafone, being prodrugs of the benzodiazopine variety. At first, it was in attempt to make a complete list of water-soluable (i.e. injectable) benzos, and through such I came across these.

Seeing as they are metabolized into active benzos once in the body, but don't cause any direct effect on benzo receptors (from Wiki on the former):

Rilmazafone has no effects on benzodiazepine receptors itself, but once inside the body is metabolised by aminopeptidase enzymes in the small intestine to form the active benzodiazepine 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide.
Source

I wonder how this would affect physical addiction. I cannot really seem to find any literature on this - how a benzodiazopine prodrug would contrast with more typical benzos when it comes to a tolerance and withdrawal symptoms. It's mainly curiosity, but has anybody ever looked into these drugs before, or prodrugs of the benzo variety in research? Or sampled?

I understand that fosazepam was engineered to be a (good) water-soluble derivative of diazepam, but why the need for a pro-diazepam as well? If it has nothing to do with dependency, why would such be administered as compared to alternatives?
 
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MurphyClox

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I wonder how this would affect physical addiction. I cannot really seem to find any literature on this - how a benzodiazopine prodrug would contrast with more typical benzos when it comes to a tolerance and withdrawal symptoms.

I would think that there are no major differences with regard to physical addiction. IIRC, the open-ring prodrug was developed mainly to overcome solubility problems of the classical closed-ring benzos.

After enzymatic ring closure (which happens quite early after uptake; partly in the intestines, partly in the liver) those compounds can be considered like the regular benzos.

- Murphy
 

Kae deNine

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does anyone know what the metabolites are for the Active metabolite of Rilmazafone???
as in, if taken, would you come up positive on 1) A dipstick benzo drug test, and 2) a gc/ms benzo drug test ...... meaning looking for all regular benzo metabolites I.E. diazepam, nordiaz, oxazepam, temazepam, clonazepam metabolites, etc....

any info would be appreciated. And yes, I've searched myself looking for info on this, and haven't been able to come to any definitive conclusions.

Also, the active metabolite of Rilmazafone is: 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a][1,4]benzodiazepine-2-carboxamide.
As far as i know, it doesn't have a generic or shorter name.... please correct me if im wrong. But, as i hypothesize, I AM inclined to believe that this WOULD trip a benzo drug test seeing as it has as its skeleton, just like many of the popular mainstream benzo's, the 1,4-Benzodiazepine structure.

And again, please correct me if i am wrong in any of my assumptions or information. I am going on the best of my knowledge and gathered information. Thanks!
 

serotonin2A

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The desglycylated cyclic metabolite (8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a][1,4]benzodiazepine-2-carboxamide) is usually called M1. As far as I know no one has bothered to assign an INN (generic name) because it isn't an existing drug or an article of commerce. GC/MS could certainly be used to identify M1 and distinguish it from other benzodiazepines.

In terms of the metabolites of M1, here is what is known:

M4 - major metabolite in plasma and urine = 8-chloro-6-(2-chlorophenyl)-4H-1,2,4-triazolo [1,5-a][1,4]benzodiazepine-2-carboxylic acid
M3 - N,N-didesmethyl-M1 = 8-chloro-6-(o-chlorophenyl)-4H-1,2,4-triazolo-[1,5-a] [1,4] benzodiazepine-2-carboxamide
M2 - N-desmethyl-M1 = 8-chloro-6-(o-chlorophenyl)-N-methyl-4H-1,2,4-triazolo[1,5-a] [1,4] benzodiazepine-2-carboxamide
MA - 8-chloro-6-(o-chlorophenyl)-N-hydroxymethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide
MD - 8-chloro-6-(o-chlorophenyl)-N-hydroxymethyl-N-methyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide

http://www.ncbi.nlm.nih.gov/pubmed/3428781
http://onlinelibrary.wiley.com/doi/10.1002/bdd.2510140402/pdf
http://www.ncbi.nlm.nih.gov/pubmed/3454653
http://www.ncbi.nlm.nih.gov/pubmed/2886322
 

Ballz_Trippington

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I'm very Interested in Rilmazafone... anyone have any first hand reports ?
I wonder how this compares to most other benzos... seems like this one would be easy to import anywhere because it's not actually scheduled anywhere and not active until you injest it.
I've read a few reddit reports buy has no one on bluelight got any experience with this one????
 

Fertile

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The imidazo sub-class of benzodiazepines & pyrazolo analogues are all capable of producing water-soluble addition salts.


It's interesting that alprazolam ring-opens to it's parent benzophenone in acidic conditions. I wonder HOW acidic it has to be and would it work similarly for something like flualprazolam.

After all, the benzophenone is inactive - one would need to increase the pH using external measures to produce something psychoactive.
 

cigea244544

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In Japan, rilmazafone is considered the weakest benzodiazepine sleep medication (´・ω・`)
Until some years ago, it seemed that elderly people were taking this medicine.
I was once on rilmazafone but could not sleep (>_<)
 

Fertile

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Because the body has to hydrolize the aminoacetic acid.

If someone could remove that group, the compound would be much faster acting although I cannot comment on the potency of the active. What I find amazing is that mephenazpam has never turned up. It's legal & can be made from phenazepam in 1 step & 99% yield. Mephenazpeam is almost identical to diclazepam - the most potent benzo I know of.


Now as far as I know, the above has never been made and as such is uncontrolled. We DID produce a5 gram sample but I did not sample it. We wished to compare it to diclazepam and the consensus was that the two were nigh on identical. Of course, the N-methylation of the amide using trimethyl phenyl ammonium bromide was only introduced in 2021 so we had to start with the appropriate benzophenone (lots of work).

What surprises me is that seemingly nobody has tried diclazepam. It's duration and that of it's active metabolites is over a week i.e. if you dose once a week, the level in your body will slowly increase. It was convenient (2mg BID was more potent than 30mg diazepam TID) and it had potent muscle relaxant properties... I mean people felt 'bendy' after just 1 x 2mg tablet.
 
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