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Simplest Opioid I've ever seen

C

clubcard

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Apr 12, 2013
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Not strong (good), high TI (good), no nasty metabolites (good) 1-step synthesis (for a pethidine potency compound) - much safer than U47700, a compound that will get banned REALLY fast, I hope.

This compound was discovered by Russian scientists in 1954 & rediscovered in the US in 1969

Ref - http://www.ncbi.nlm.nih.gov/pubmed/5351480

The paper says '29 was the most potent of the series. It had an ED50 of 16mg/Kg which is roughly twice that of morphine sulfate when determined under similar conditions. LD50 of 238mg/Kg.

It overlays 3,3-dimethyl propinyloxy piperidine (7-10 x pethidine) and is about as potent as pethidine BUT isn't a prodrug - nobody can modify it to make it stronger. I like it because it's an examples of conformational isomerism, a lesson that labile compounds have much less affinity than (semi)rigid analogues. If I get the chance, I may try adding the 3,4-dichloro derivative. Of course, that would be FAAAARRRR from a single-step synthesis; certainly too much for any RC chemist.
 
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I swear it says LD50=85mg/kg in the PDF link. Maybe it's blurred.

If we're talking about an effective and safe RC opioid, then what would the dosage be? I'm guessing they did the tail flick test for mice. Can anyone comment on how much higher or lower the euphoric dose would be in humans.

Is there a possibility that this might have slight stimulant or anorexic properties?
 
It's like pethidine without the toxicity of N-desmethyl pethidine (a DRI/NRI0
 
There is a chance that the O & N could interact in a near-minimum energy state giving it DRI properties. That's the problem, they only test for 1 activity.

Nobody knows the activity in man. A test in a mammal would be of supreme interest from the safety front. Dogs are usually the unlucky victims... actually, that far back, monkeys/apes would be used, which is unconscionable to me. I've always believed in self-testing on the basis of 'if anyone is hurt by this stuff, it's me', common until the 1960s, Bentley nearly wiped out his whole lab when a teapot had it's contents stirred by a glass rod previously used to make some super-potent agonist. I can still remember people smoking in labs. People just turned their head away as they opened ether containers - no H&S laws; just common sense (which as you can see, are in acute short supply).
 
Whoever built the Wiki page - the compound is mentioned in the 1969 Annual Journal of Medicinal Chemistry page 34 compound 28.

My only reason for highlighting this is that it's MUCH safer than the fentanyl analogues and U47700. Those compounds have all killed many people.


FREEDOM OF SPEECH
 
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That was Nagelfar who as always forgets to enter data in the infobox and ignores WP:CSDG =D
 
I don't know - I mean, it's simple to make and as safe as we can expect - better than messing with fentanyl analogues of U477700
 
Found a interesting paper on cytotoxicity of closely related compounds.

Evaluation of cytotoxicity of some mannich bases of various aryl and arylidene ketones and their corresponding arylhydrazones

Dimethylaminopivalophenone itself was not evaluated sadly.

However, attempts to prepare 2,2-dimethyl-3-dimethylamino-1-phenyl-1-propanone hydrochloride led to a product whose proton nuclear magnetic resonance ('H NMR) spectrum was consistent with this structure but whose elemental analysis was unsatisfactory. Hence, this product was not submitted for cytotoxic evaluation but was converted satisfactorily to the corresponding hydrazone, 1e.
Click to expand...
 
The high-potency opiates all seem to have a high specific binding to the mu1 receptor which is why they are so dangerous - to get a buzz, you need to tickle the mu2 receptors. Hence the great death-toll due to them. There are a couple of exceptions which are mu/delta agonist. The mixture gives the high potency but the delta receptor means respiratory failure is most unlikely (but strong opiates are out, for me at least).

Back to the opioid in question. It overlays:

'1,3,3-Trimethyl-4-Phenyl-4-(Propionyl)Piperidine' by F.R. Ahmed, G.F. Laws, A.E. Madani, and A. F. Casy - J. Med. Chem. 1985,28, pages 1947-1949

The interesting that having 2 methyl groups at the 3 position makes a STRONGER opioid than beta prodine.

I also think People should carefully read about Phenampromide & Propiram. I would BET that replacing the N,N-dimethylamine moiety can be replaced with a piperidine. Other N substitutions make stronger compounds. One of them is x132 the parent BUT it's TI makes it useless. The morpholine could bring a superior effect.

FREEDOM OF SPEECH
 
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clubcard said:
The high-potency opiates all seem to have a high specific binding to the mu1 receptor which is why they are so dangerous - to get a buzz, you need to tickle the mu2 receptors. Hence the great death-toll due to them. There are a couple of exceptions which are mu/delta agonist. The mixture gives the high potency but the delta receptor means respiratory failure is most unlikely (but strong opiates are out, for me at least).

Back to the opioid in question. It overlays:

'1,3,3-Trimethyl-4-Phenyl-4-(Propionyl)Piperidine' by F.R. Ahmed, G.F. Laws, A.E. Madani, and A. F. Casy - J. Med. Chem. 1985,28, pages 1947-1949

The interesting that having 2 methyl groups at the 3 position makes a STRONGER opioid than beta prodine.

I also think People should carefully read about Phenampromide & Propiram. I would BET that replacing the N,N-dimethylamine moiety can be replaced with a piperidine. Other N substitutions make stronger compounds. One of them is x132 the parent BUT it's TI makes it useless. The morpholine could bring a superior effect.

FREEDOM OF SPEECH
Click to expand...

Hey cc, ever come across a Mu3 selective (at the expense of μ1 & μ2 subtypes) opioid? The esters of morphine, it's metabolites like M3G etc., seem to have academia published to validate morphine itself is only a prodrug to Mu3 because only its esters (ethers too maybe?) of morphine agonize μ3. 6-MAM also, which may add to diacetylM's difference from morphine, one more state that undergoes μ3 agonism and one more immediate before morphine at that.) That, and kappa antagonism with supposedly makes any mu agonism safer due to the automatic nervous system not become as sedate, breathing not being as shallow/depressed.
 
possibly mu3 is just a genetic variation - the fact so little work has been done on it suggests that nobody thinks it's a winner.

If the dimethyl amine of this simple opioid, the effect of the piperidine needs looking at. THAT could well be a bigger winner for many reasons.
 
clubcard said:
possibly mu3 is just a genetic variation - the fact so little work has been done on it suggests that nobody thinks it's a winner.

If the dimethyl amine of this simple opioid, the effect of the piperidine needs looking at. THAT could well be a bigger winner for many reasons.
Click to expand...


I believe mu3 is due to a posttranslational modification and is only found in immune cells.
 
Anyone noticed that 3,3-dimethyl analogue of phenampromide is a lot more potent as is 3,3-dimethylpromide? And 1,3,3 trimethyl peridine is much more potent tham MPPP? I can find examples of 3,3 disubstituted fentanyls. Basically, having the CORRECT methyl in place increases the potency BUT the wrong methyl has no bad effects. In short, phenapromide acts like fentantyl - the 4-benzyl is x60 morphine.

FREEDOM OF SPEECH
 
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Esters? No, all are amides BUT consider the 3,3 in relation to 3,3 dimethyl fentanyl.
 
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