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Nocaine: From tropane to piperidine

E

EN21

Bluelighter
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Nov 17, 2005
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I recently listened to a lecture from Kozikowski. Anybody interested in it?
 
One additional thing kept in my mind: Kozikowski mentioned in his lecture that the NOR compound of nocaíne would probably the most promising compound if you want to bring it on the streets. (Funny guy!)
But I have no ideas, why he favoured this compound.
 
Apparently for some reason the NH compound is less resistant to ester hydrolysis than the NMe compound. This means that the compound lasts roughly twice as long. The NH analog is also more potent than the NMe analog by a significant margin although N-demethylation will occur in-vivo to some extent at any rate. Also his lazy Nocaine is suppose to be a locomotor activity (LA) stimulant after N-demethylation.

You got the refs though. I have read those papers but cant currently access them or i'd make upload links for you to read.
 
comparison with epibatidine

I wonder about the similarity to epibatidine, a potent nicotinic agonist with strong narcotic effects.
 
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Sorry! of course!
Here are the corrected formulae, but nevertheless I find the similarity of the skelettons remarkable.
Was epibatidine ever tried recreationally? Anybody heard of it?
 
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This should help explain in more detail the research being covered in the lecture you went to. Kinda suprised he picked the Paxil analog since in the journal article it is documented to be almost without activity.

Another interesting find is that using a 'linker' to connect two of the 'Nocaine' isomers (or two of the other trans isomers) led to the elucidation of some good and impressive SSRI's etc.

jm000552sn00001.gif
 
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It seems like im just communicating to myself on this one but if Kozikowski seriously believes that Nor-Nocaine is a would sell well on the street then it appears that a relatively pure norephedrine inhibitor is all that is required (ie. attenuated DAT and SERT affinity). This is certainly interesting if it is correct. There are very few people who have established the reputation of Kozikowski. Ivy Carrol is on the same parable but these guys stand out from the rest of the crowd. Take what Kozikowski says as Gospel.
 
I don´t knew whether he tasted it itself, or his rats. So I don´t know what made him to assume it, maybe only from the behavior results of his rats, or own experimentations with it?
 
Hi, Smyth!
I just found a little time to have a look in the J.M.C. article. The findings concerning the NOR-nocaine do not really fit to Kozikowskies words in the lecture. I hardly can imagine what should be the clue of a compound that produces " biphasic effects consisting initial locomotor depreddion followed by a delayed locomotor stimulation" that acts significant longer than coce itself.
 
hexahydro-ßcarbolines

As you mentioned elsewhere concerning ß-carbolines: "Parallel to Mitragynine, i'm actually very interested in disrupting the indole aromaticity by oxidation with Pb(OAc)4."
I admit, it could really be very interesting to disrupt the aromaticity indole moiety of a ßC. But I am not sure that we both meant the same. I mean reduction, not oxidation, and I can hardly imagine that Pb(OAc)4 is the chemical that could do that job. But when you have references for this reaction, it would be great. The possible problem that I see is the stereochemistry of those compounds. In theory there can be 4 isomers, two with a trans connected ring and two with a cis connection. I attached the formula of the "possible" right isomer.
Have a nice weekend!
 
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7-OHM refs can be found online. Below is just one example.

http://www.drugs-forum.co.uk/articles/kratom-alkaloids.pdf

No, reduction of alkenes was not what I was referring to. I mean you have to be careful handling THP's dont you.

http://patft.uspto.gov/netacgi/nph-...chmann+AND+tramadol&RS=Buschmann+AND+tramadol

I reckon that 5- or 6- methoxyl-DMT followed by hydroxylation (oxidation) at the 7-position with Pb(OAc)4 might yield some analgesic tryptamines.

This is just a guess though.

For instance replacing the ketone in methadone by a methyl-ester does not work as expected. Thus SAR's cannot be considered totally predictable.
 
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For instance replacing the ketone in methadone by a methyl-ester does not work as expected. Thus SAR's cannot be considered totally predictable.
Click to expand...

There's no good reason to expect it to work, drugs like dextromoramide (that is an amide of pyrrolidine using a carboxylate group where the C=O in methadone would be) are active, but going from a 3 carbon chain to a carbon-oxygen-carbon chain is a big leap for the diphenylheptylamines. what you've proposed is a very wide ranging SAR type study - mostly it would be trying different amines in place of dimethylamino in methadone, or altering the length of the 7 carbon chain
 
Here are my personal notes from Kozikowskis lecture:
Nocaine is more potent but less stimulating, it antagonizes the locomotive effect of cocaine and also meth. It has a lower addiction potential than coke. More rapid onset. The acid is inactive, the Nor compound more active (sell on streets)
Norepinephrine seems not to be involved in the self administration activity. Nocaine may serve as an antidepressant?
-I know that is not much
 
I remember reading an article recently in the Journal of Medicinal Chemistry where they mentioned nocaine ((+)-CPCA) was going to be moved up to human trials. Also from the most recent data nocaine seems to have high affinity for DAT (about twice cocaine's), quite a bit less affinity for NET (about half of coke's), and basically zero affinity for SERT. It was also mentioned to be cocaine-like on coke trained rats but also a bit meth like. I've been wondering what the difference is in terms of something being judged more meth-like or coke-like, subjectively.

I read this stuff all Christmas break at work. Fascinatingly scandalous information.
 
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