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Benzimidazoles

Giza

Giza

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Aside from Etonitazene, Clonitazene, and Nitazene, is there any other Benzimidazoles or even analogs of the above worth investigation as supra potent opioid mu agonists? Un-specifically-scheduled... of course :)

and does anyone know the mcg/kg approximate doses used for Etonitazene, Clonitazene and Nitazene?
 
There are a whole series of substituted benzimidazoles that have mu agonist activity - they all differ in the group replacing the ethoxy group of etonitazene (or the chloro group of clonitazene). None are as potent as etonitazene, but quite a few are within an order of magnitude of potency

59655opiate_grps_-_benzimidazoles.JPG


Any alteration to the diethylaminoethyl group attached to one of the nitrogens of the benzimidazole nucleus pretty much abolishes opiate activity. Reduction of the nitro group severely attenuates any opiate activity.

From what I can remember, other active groups (for replacing the ethoxy/chloro group) are methoxy & bromo (probably all haogen replacements). Due to their similarity, ethylthio and methylthio might be active, but that's just educated guesswork
 
Here is what I have on record regarding these compounds:

G. Bromig tested the 4'-chloro and 4'-methoxy derivatives of etonitazene in human surgical patients. The 4'-Cl was found to be 1/3 as active as morphine and appeared useful as an analgesic, while the 4'-MeO analog was found to be 10 times more active than morphine and also very toxic.
Bromig G., Klin. Wochenschr. 36, 960 (1958)

In morphine abstinent addicts in withdrawal, 1 mg etonitazene orally replaces 60 mg morphine subcutaneously.
Fraser F.H. et al.
Addictiveness of new synthetic analgesics. Add 2, Min. 21st Meet., Comm. Drug Addiction and Narcotics, Natl. Res. Council, Natl. Acad. Sci., Washington, D.C:, 10-11 Jan 1959

Another benzimidazole opioid is bezitramide. The oral dose is 5 mg and it's rather long acting:

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PS: somewhere on Erowid there's still the archive of Rhodium's PDF files, and amongst them several on etonitazene-type opioids with SAR data etc.
 

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I've read in several sources that they are clearly shorter acting than morphine.
 
Those PDF's on rho's, all but 1 are in I beleive russian, could be a different language, regardless, they are of no use unless somone here speaks russian... :(
 
Well, I now notice that I made a mistake with the bezitramide structure. What's depicted ist the structure of the active metabolite. Bezitramide itself has a propionyl gruop on the free benzimidazolone nitrogen.

There's a very interesting relation between neuroleptics and opioids as can be seen in the chart below. Depending on the "tail" of the molecule it's either a neuroleptic or an opioid:

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Because there's a literature value for it's affinity for the µ-opioid receptor, and that's pretty low.
 
Is this the end of the thread? I still have some unanwered questions though. Qustions like if the Nitazene analog is shown on Rhodiums web page then why is it not a scheduled compound? Why is no reference given to the potency of the compound when the poster is clearly insinuating that people should make it? From what I understand, it looks like only the eto' analog is anygood.
 
^ Clonitazene & etonitazene are controoled drugs in the UK. The reason that no others have been added (or a derivatives paragraph like there is for pethedine & fentanyl) is that no-ones ever really attempted a clandestine synthesis with an aim of selling it as a heroin replacement.

Apparently the methoxy compound (metonitazene?) and the bromo coumpound (again, bronitazene?) are fairly active mu agonists. If I remember correctly there are also other compounds where the ethoxy group has been replaced that are active, only with an order of magnitude drop in potency (but when you consider that etonitazene is rated as something like 1000x the potency of morphine, that's not really a problem).

Maybe it's just a bastard to synthesise
 
Maybe it's just a bastard to synthesise
Click to expand...

Quite possibly because even though mentally the synthesis seems quite workable, no yields are quoted in the patent.

I'd just like to know if there is any journal articles on this compound. Like SAR studies on changing the 4-phenyl subsitituent and modification of the alkyl groups at the nitrogen.

However if I go into espace and type "benzimidazoles AND analgesic" I get some other shit to look at. Most of it are GBR patents published by a Swiss group called CIBA.

How the fuck is someone supposed to lay their trust in some patents that have been derelict for a good 40 years, where yields and relative potency of the resultant compounds is not even discussed?

Damn malicious coding on my computer is slowing me down.
 
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C6H6 said:
There's a very interesting relation between neuroleptics and opioids as can be seen in the chart below. Depending on the "tail" of the molecule it's either a neuroleptic or an opioid:

attachment.php
Click to expand...

That's very interesting, are there such relations between more common opioids (morphine, heroin, methadone, codeine, oxycodone...) and known neuroleptics?

Are Haloperidol and loperamide named like that because of there relationship?
 
To my observation a "lo" in the name usually denotes a chlorine somewhere. Loratadine, Desloratedine, Lorazepam, Loprazolam, Loperamide, Clonazepam, Clotiazepam, Haloperidol, Diclofenac, Baclofen... off the top of my head, all contain Chlorine somewhere or another, and I believe they are all on a ring.

I could be playing connect-the-dots though...
 
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