You are very clued up on this. I'm afraid I don't know the ins and outs of it.
But it did say he had 13 compounds in a previous article. We only need 1 for the product to be released initially. Ball rolling so to speak.
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Professor Nutt's magic jizz (Sentia)
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But it did say he had 13 compounds in a previous article. We only need 1 for the product to be released initially. Ball rolling so to speak.
AlsoTapered
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Yeah - the problem is that a synthetic alcohol replacement is a drug. It's going to be subject to the same safety regime that a candidate medicine would undergo. After all, it's not like a pharmacist will be involved so it would have to be proven safe beyond all doubt.
That kind of testing costs simply HUGE amounts of time and money.
I took the money because I pointed this out and they didn't really have an answer. The EU will require EU testing, the US will require US testing and so on.
Believe me, pyeyzolam IS much safer than ethanol... except if you MIX it with alcohol. Designing something that won't do that... I don't know how you would do it. I did point out that their are some natural compounds that act like disulfiram (Antabuse) but apparently that's essentially allowing a buildup of acetaldehyde in the body and is itself dangerous which is why disulfiram is no longer in use.
I don't think a warning label would cut it - not if it's a potentially fatal interaction.
That kind of testing costs simply HUGE amounts of time and money.
I took the money because I pointed this out and they didn't really have an answer. The EU will require EU testing, the US will require US testing and so on.
Believe me, pyeyzolam IS much safer than ethanol... except if you MIX it with alcohol. Designing something that won't do that... I don't know how you would do it. I did point out that their are some natural compounds that act like disulfiram (Antabuse) but apparently that's essentially allowing a buildup of acetaldehyde in the body and is itself dangerous which is why disulfiram is no longer in use.
I don't think a warning label would cut it - not if it's a potentially fatal interaction.
£15m to crack the US market I read. We wait with baited breath.
BadBoy377
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How you pronouncing that? Like pie-eye-zolam... Kinda like it does what it says on the tin
Love your work, mate.
AlsoTapered
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How you pronouncing that? Like pie-eye-zolam... Kinda like it does what it says on the tin
Love your work, mate.
You sir, are the first person to get that joke.
It's not novel - Xanax means 'exit anxiety', Quaalude means 'quiet interlude' and Valium from the Latin 'vale' meaning 'good night'.
So calling a drug that gets one drunk... well pie eyed is what my mother termed it, so it's in her memory.
Nutt's answer about the mixing of alcohol and synthetic alcohol. 4 years ago though
Bleaney
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This whole venture could go various ways.
Based on the verdicts encountered so far, it's likely to be a complete flop, that won't gain any traction.
On the other hand, if they manage to improve the formulation, it cold go on to be quite succesful.
I can only ever see it as being a pretty niche thing though, I don't think it will ever become a huge mass market commercial smash hit.
I wonder what his motives are? To prove a point? Is there any point though, seeing as anything truly and effectively psychoactive is not legal.
Although some natural products do skirt around this legislation. I swear Valerian is effective, Ashwaganda is supposed to be too., so I suppose I shouldnt be too negative and pessimisitic until the next wave of products have been unleased upon us.
Based on the verdicts encountered so far, it's likely to be a complete flop, that won't gain any traction.
On the other hand, if they manage to improve the formulation, it cold go on to be quite succesful.
I can only ever see it as being a pretty niche thing though, I don't think it will ever become a huge mass market commercial smash hit.
I wonder what his motives are? To prove a point? Is there any point though, seeing as anything truly and effectively psychoactive is not legal.
Although some natural products do skirt around this legislation. I swear Valerian is effective, Ashwaganda is supposed to be too., so I suppose I shouldnt be too negative and pessimisitic until the next wave of products have been unleased upon us.
I think the market is crying out for something like this to be honest.
Non alcoholic is just a soft drink, real alcohol leads to problems. We want something in the middle.
Fastest growing section of the drinks industry is the non alcoholic bit.
AlsoTapered
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I can assure you that pyeyzolam really does accurately reproduce the positive effects of alcohol
-Anxiolytic
-Increased sociability
-Improved mood
-Non-vascular muscle relaxant
Without the negative effects of alcohol
-Disinhibition
-Loss of judgement
-Anterograde amnesia
-Mood lability
-Ataxia
-Nausea/Emesis
-Physical dependence
As well as the physical damage of alcohol which in it's acute phase we recognize as a hangover but in it's chronic phase includes Korsakov syndrome, fatty liver disease, heart disease, kidney disease and so on.
It turns out that alcohol primarily acts on the a1 and a5 subunits of the GABA receptor and it's the a1 activity that causes most of the negative symptoms of alcohol (think Z-drugs which are all a1 selective) and a5 activity that produces all of the positives (unless people WANT disinhibition, loss of judgement and/or amnesia, I suppose). We know how to simulate the good parts of alcohol and understand why their are positive and negative effects.
No, I'm 100% sure they have at least 3 because I sold pyeyzolam to Alcarelle (I was offered cash or shares and took cash because had no faith in their business model - too many questions they had no answers for). BUT if pyeyzolam is mixed with alcohol, it multiplies (not adds) to the effects of the alcohol so while 25mg of pyeyzolam is more or less like drinking a bottle of wine. If you drink a bottle of wine after 25mg of pyeyzolam you WILL black out and that is dangerous.
Their is no getting around that.
The only failing of pyeyzolam was it's dose-response curve. Up to about 20mg it does nothing and then from 20-30mg it goes from a glass of wine to two bottles of wine. BUT we discovered why and tested it. Alcohol binds to the a1 & a5 subunits at the junction of the b1, b2 and b3 subunits and so you need a candidate that isn't beta selective. Step one was to have pyeyzam (the 1,5 analogue of pyeyzolam) made and tested and alone it wasn't very active. It took 40mg for anything to happen and then the same glass of wine level BUT it had a plateau in it's effects. However much you take (and we did take a lot) it only ever got to the same as around two or three glasses of wine.
BUT if you mix pyeyzolam and pyeyzam in the appropriate proportions, you end up with a product that will emulate anything from a glass of wine to a bottle of vodka.
So the problem of emulating alcohol is solved. As people may know, like pyrazolam both pyeyzolam and pyeyzam are excreted by the body unchanged. This was a FEATURE of the design. Medicinal chemistry is littered with medicines that a small proportion of the population metabolized in a different manner and produced toxic metabolites. The most famous is the antibiotic Trovan (trovafloxacin) which Pfizer trialled on children in Africa and turned into a disaster. But their are actually many more - it's just that pharmaceutical giants are able to cover up most cases. So a medicine that isn't metabolized has a distinct advantage.
But the problem with the alcohol mimic I mention is that it requires TWO drugs. Pyeyzolam is a5b1y2 selective while pyeyzam binds to both a5b2y2 and a5b3y2. So BOTH of them would have to go through testing essentially doubling the cost (I've worked with Huntingdon Life Sciences and so I do know how medicines are tested).
The breakthrough I made (and won't be sharing publicly) is that it's possible to produce something in-between pyeyzolam and pyeyzam that isn't beta selective. Now the modelling of ALL the different subtypes of the benzodiazepine sites was carried out by one James T. Cook at UWM in the US.
Above is a VERY good resource. Cook essentially spent 30+ years researching the benzodiazepine site and almost all of his students worked on 3DQSAR analysis.
I wouldn't say my single-drug solution is some great feat of medicinal chemistry but rather a bit of lateral thinking. Tautomers and more specifically mesoionic compounds hadn't been explored but it's possible to design a tautomer that places the pendent aromatic in the same position as a 1,4 benzodiazepine and in the same position as a 1,5-benzodiazepine.
I was kind of tipped off by looking into French research into 4-phenyl-4H-benzo[d][1,3]oxazin-2-amines (such as Etifoxine). I couldn't work out why the N-ethyl was the most active by a HUGE margin until I realized that of course, it's a tautomer.
Frankly, I believe the most facile path is via China. Their one party system certainly has it's failings but if an existing production/distribution/retail/marketing/legal framework can be adapted for a new product (I mean the alcoholic drinks industry) then it seems to me they can do it. Jobs, taxation and duty are, in truth, more important to politicians than safety so if overnight the ethanol were replaced by a safe mimic, essentially nothing would have to change apart from the list of ingredients on the packaging.
Sorry to bang on about it but GABA Labs seem to think they can begin begin as a niche product. I totally disagree. I think it needs a government to DECIDE that alcohol is dangerous and impose a change. Not possible in a democratic nation. InBev and the other massive brewing companies will fight to keep alcohol as they are defending a market share.
I thought their sales were falling due to youth of today going low and no?? Also the older real drinkers dying out or having been told to stop for health reasons.I can assure you that pyeyzolam really does accurately reproduce the positive effects of alcohol
-Anxiolytic
-Increased sociability
-Improved mood
-Non-vascular muscle relaxant
Without the negative effects of alcohol
-Disinhibition
-Loss of judgement
-Anterograde amnesia
-Mood lability
-Ataxia
-Nausea/Emesis
-Physical dependence
As well as the physical damage of alcohol which in it's acute phase we recognize as a hangover but in it's chronic phase includes Korsakov syndrome, fatty liver disease, heart disease, kidney disease and so on.
It turns out that alcohol primarily acts on the a1 and a5 subunits of the GABA receptor and it's the a1 activity that causes most of the negative symptoms of alcohol (think Z-drugs which are all a1 selective) and a5 activity that produces all of the positives (unless people WANT disinhibition, loss of judgement and/or amnesia, I suppose). We know how to simulate the good parts of alcohol and understand why their are positive and negative effects.
No, I'm 100% sure they have at least 3 because I sold pyeyzolam to Alcarelle (I was offered cash or shares and took cash because had no faith in their business model - too many questions they had no answers for). BUT if pyeyzolam is mixed with alcohol, it multiplies (not adds) to the effects of the alcohol so while 25mg of pyeyzolam is more or less like drinking a bottle of wine. If you drink a bottle of wine after 25mg of pyeyzolam you WILL black out and that is dangerous.
Their is no getting around that.
The only failing of pyeyzolam was it's dose-response curve. Up to about 20mg it does nothing and then from 20-30mg it goes from a glass of wine to two bottles of wine. BUT we discovered why and tested it. Alcohol binds to the a1 & a5 subunits at the junction of the b1, b2 and b3 subunits and so you need a candidate that isn't beta selective. Step one was to have pyeyzam (the 1,5 analogue of pyeyzolam) made and tested and alone it wasn't very active. It took 40mg for anything to happen and then the same glass of wine level BUT it had a plateau in it's effects. However much you take (and we did take a lot) it only ever got to the same as around two or three glasses of wine.
BUT if you mix pyeyzolam and pyeyzam in the appropriate proportions, you end up with a product that will emulate anything from a glass of wine to a bottle of vodka.
So the problem of emulating alcohol is solved. As people may know, like pyrazolam both pyeyzolam and pyeyzam are excreted by the body unchanged. This was a FEATURE of the design. Medicinal chemistry is littered with medicines that a small proportion of the population metabolized in a different manner and produced toxic metabolites. The most famous is the antibiotic Trovan (trovafloxacin) which Pfizer trialled on children in Africa and turned into a disaster. But their are actually many more - it's just that pharmaceutical giants are able to cover up most cases. So a medicine that isn't metabolized has a distinct advantage.
But the problem with the alcohol mimic I mention is that it requires TWO drugs. Pyeyzolam is a5b1y2 selective while pyeyzam binds to both a5b2y2 and a5b3y2. So BOTH of them would have to go through testing essentially doubling the cost (I've worked with Huntingdon Life Sciences and so I do know how medicines are tested).
The breakthrough I made (and won't be sharing publicly) is that it's possible to produce something in-between pyeyzolam and pyeyzam that isn't beta selective. Now the modelling of ALL the different subtypes of the benzodiazepine sites was carried out by one James T. Cook at UWM in the US.
Above is a VERY good resource. Cook essentially spent 30+ years researching the benzodiazepine site and almost all of his students worked on 3DQSAR analysis.
I wouldn't say my single-drug solution is some great feat of medicinal chemistry but rather a bit of lateral thinking. Tautomers and more specifically mesoionic compounds hadn't been explored but it's possible to design a tautomer that places the pendent aromatic in the same position as a 1,4 benzodiazepine and in the same position as a 1,5-benzodiazepine.
I was kind of tipped off by looking into French research into 4-phenyl-4H-benzo[d][1,3]oxazin-2-amines (such as Etifoxine). I couldn't work out why the N-ethyl was the most active by a HUGE margin until I realized that of course, it's a tautomer.
Frankly, I believe the most facile path is via China. Their one party system certainly has it's failings but if an existing production/distribution/retail/marketing/legal framework can be adapted for a new product (I mean the alcoholic drinks industry) then it seems to me they can do it. Jobs, taxation and duty are, in truth, more important to politicians than safety so if overnight the ethanol were replaced by a safe mimic, essentially nothing would have to change apart from the list of ingredients on the packaging.
Sorry to bang on about it but GABA Labs seem to think they can begin begin as a niche product. I totally disagree. I think it needs a government to DECIDE that alcohol is dangerous and impose a change. Not possible in a democratic nation. InBev and the other massive brewing companies will fight to keep alcohol as they are defending a market share.
AlsoTapered
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In some nations yes, in other nations no.
Those large brewing conglomerates line InBev are moving into developing nations in a big way.
Russia still has a massive problem with alcohol but there younger people are switching from vodka to (strong) beer. Under Russian law any drink containing less than 10% ABV is legally a FOOD so they are most certainly attempting to hide the issue.
But then Russia officially doesn't have a single HIV+ person in the entire nation and drug use isn't monitored beyond fatalities.
It WAS interesting to discover that it's possible to produce compounds that produce a subset of alcohol's effects.
It was also possible to selectively emulate alcohol's serotonergic & dopaminergic effects. This proved to be very different to alcohol but we considered it to be too addictive. Not dependence-forming but addictive. Pynazolam LOOKS like it will be a typical benzodiazepine BUT only appears to alter extracellular monoamine levels.
A friend who is old enough to remember Mandrax (methaquaalone) said that pynazolam produced very similar effects but was less sedating. It was pretty potent as well. 10mg he estimated to be roughly as strong as 300mg of methaqualone.
Those large brewing conglomerates line InBev are moving into developing nations in a big way.
Russia still has a massive problem with alcohol but there younger people are switching from vodka to (strong) beer. Under Russian law any drink containing less than 10% ABV is legally a FOOD so they are most certainly attempting to hide the issue.
But then Russia officially doesn't have a single HIV+ person in the entire nation and drug use isn't monitored beyond fatalities.
It WAS interesting to discover that it's possible to produce compounds that produce a subset of alcohol's effects.
It was also possible to selectively emulate alcohol's serotonergic & dopaminergic effects. This proved to be very different to alcohol but we considered it to be too addictive. Not dependence-forming but addictive. Pynazolam LOOKS like it will be a typical benzodiazepine BUT only appears to alter extracellular monoamine levels.
A friend who is old enough to remember Mandrax (methaquaalone) said that pynazolam produced very similar effects but was less sedating. It was pretty potent as well. 10mg he estimated to be roughly as strong as 300mg of methaqualone.
Yea, I don't think Russia is the target market. They drink TO GET DRUNK..
USA followed by Asian and Europe is target, UK of course too.
As a UK resident I will.be looking at Ireland with interest cause it's a short flight. The Guinness is absolutely beautiful over there ( even the non alcoholic stuff) so I'd be hopping over there if UK shuns it but EU doesn't.
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lol leave it to the ruskies
BadBoy377
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Sounds like the best job in the world, mate.
AlsoTapered
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Like all of these things, 99% of the work was the dull stuff. ANYONE can download a free software package and happily scribble structures or use free online 'drug likeness' calculations but if you can't ACTUALLY make it, it's of no value whatsoever. Pyrazolam was only produced as a convenient precursor for pyeyzolam, pynazolam and pysylozam.
The only difference between those four is the 8-substituent.
8 Br- is pyrazolam
8- CHC- is pyeyzolam
8 NO2- is pynazolam
8-SiCH3 is pysylozam
The last one of these didn't get past animal studies so I cannot report on it's subjective effects. While the trimethyl silyl moiety has found it's way into a few drug candidates, I think I'm correct in saying that their is no medicine that contains an organo-silicon moiety. In this case we noted that it produced significant toxic symptoms in animal models and since the ethynyl had almost identical affinity data, it wasn't worth proceeding.
BTW that last one is pronounced si si lo zam. Obviously pyeyzam is pronounced pie eye zam.
Bleaney
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But what about the problem of all new psychoactive substances being rendered illegal since the NPS ban of 2016?
How can they legally use these new benzos, even if they do effectively mimic the positive aspects of alcohol, and reduce the negative aspects?
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I thought it was going to be classed as a food additive rather than a drug.
American is first and they don't have that 2016 rule I don't think??
They have G.R.A.S. ( generally regarded as safe). FDA could add it to that. If somewhere as big as USA gets it then everywhere else could follow.
This is just a guess from me btw