Gem N-pipredinyl disubstitution

[haribo1]

'morphine-like activity has been found with substitution upon the nitrogen atom of methadone. A series of 4,4-gemdisubstituted piperidinyl analogs have been found to be some 1500 times as potent as methadone, and to be quite a bit longer acting'

Taken from:[6] P. A. J. Janssen and C. A. M. van der Eycken, "The Chemical Anatomy of Potent Morphine-like Analgesics." Drugs Affecting the Central Nervous System, (A. Burger, ed.), Dekker, New York 1968, pp. 25-60.

Can anyone enlighten me as to the possible structures here?

 

[Smyth]

However no synthesis was in the paper the data was extracted from.

 

[haribo1]

Thanks for that. I already have a paper covering that one but I don't THINK it's the one Jannsen is refering to. Still, it's 212x morphine and legal!

 

[Smyth]

Yeah thats a good point, I hadn't noticed that. I wonder if he could be talking about cyclic acetals, alternatively it might have turned-out that the compounds originally discovered weren't as potent as was initially reported.

 

[haribo1]

Both good points. I suppose that spiridone IS a 4,4 gem disubstituted piperidinyl analog. I notice that it takes longer for initial effects (over methadone) at 60 minutes over 30 minutes (orally) but reaches maximum effect in 2 hours over 4 hours. Are you aware of the use of cyclizine (an antihistamine). Long ago in the UK, an opiate combination called Diconol became all the craze. The drug contained 10mg of dipipanone and 30mg of cyclizine. Apparently, shooting this gave a rush that was just amazing. Some people produced a crude analog by crushing Physeptone (methadone tablets) together with Valoid or Marezine (motion sickness pills containing cyclizine) and shooting the filtered mixture. The rush is supposed to be much better than heroin but injecting cyclizine can lead to seizures and the Diconol tablets contained colloidal silicon which screwed up veins very quickly. Cyclizine, therefore, is no longer over the counter. Its not controlled and you can buy it on the internet for 12 Euros for 100x 50mg tablets. Frightening.

 

[fastandbulbous]

Yeah the compound is technically a derivative of norpipanone (using nor in this sense is wrong, it's only supposed to removing methyl groups from nitrogen - amines - not carbon to carbon bonds: something to do with German I think). Dipipanone has a 7-carbon chain & with cyclizine is a very weird opiate. I had them prescribed - 7 days worth - many years ago and they produced some very strange visual effects, probably due to anticholinergic effects of cyclizine as well. I did try dissolving one and administering it rectally - it produced the most 'energetic' onset of any opiate that I've ever had

 

[haribo1]

Apparently, cyclizine boosts all opiates but the diphenyl heptanones especially. As I said, people were crushing physeptone & valoid tablets & shooting them. When you say 'energetic' what exactly do you mean? I know that for everyone who tried them, they instantly became the 'drug of choice'. Valoid got pulled from the shelves because, apparently, even people on oral methadone get a buzz if they shoot cyclizine on top. Heard of the new US drug 'cheese'? 8% heroin crushed into Nyquil (diphenhydramine) tablets and snorted. $2 per line, $5 per quarter gram. If someone could find an extremely potent antihistamine, you could make blotters of mixed opiate/antihistamine.

 

[hussness]

I don't think Nyquil is diphenhydramine. In my area of the US it generally contains a mixture of dextromethorphan, acetaminophen, diphenhydramine, and phenylephrine. What exactly is the interaction between opiates and antihistamines, other than countering the ichiness and increasing the sedation?
Is cyclizine fun by itself (and I don't mean fun in the sense of some moron taking 50 dramamines and hallucinating)?

 

[haribo1]

I've read some papers. Seems like it gives the initial 'flash' like injecting an opiate so if you keep shooting it when on methadone, it's like shooting heroin. It's a crack-like effect (i.e. very short, very habit forming) and is supposed to be trippy. People unable to score opiates have been known to shoot the cyclizine alone. It results in Seizures if you do too much.
Like I said, Diconol was THE Lost Ark of the Covenent to people who shoot opiates. Rare as hens teeth and, considering they only contain 10mg of a morphine strength opiate, the sold for pounds each. Trimepellenamine that was in some US motion-sickness pills and that acted similarly. Apparently late 70s vintage junkies in the US used to mix it with pentazocine (Ts and Blues) and shoot it for a heroin-like hit.
I'm sure I've read that all the 1st generation antihistamines amplify opiates to a greater or lesser extent. Like I said cheese is the latest iteration.