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Stimulants of the Future III

nuke

Bluelighter
Joined
Nov 7, 2004
Messages
4,191
Welcome to the new future stimulants thread!

What I would like to see:
Descriptions of compounds backed by patent data
Descriptions of compounds backed by data in the literature
Descriptions of compounds based upon personal experience
Analysis of the SARs of stimulants based on data

What I would not like to see:
Random molecules that you think fit into some kind of SAR
Synthesis discussion
Flaming
 
Wow we've made it far guys!
Go SotF wohooo!!

Now, on topic.
This thought I had isn't really supported by any documents nor have I found it anywhere on google and pubchem but judging by some similar existing compounds, I can't see why they couldn't be worth a go.

So we have IAP which isn't neurotoxic (and that's a big plus IMO) but lacks of dopamine realeasing potentials according to F&B, then we have Xylopropamine that seems to be more effective as a stimulant but I have no idea about it's neurotoxicity. Very little information on the net about this compound even if it was sold as an appetite suppressant.
Shulgin wrote down a few paragraphs regarding xylopropamine and othe methylated amphetamines:

2,5-Dimethylamphetamine has been looked at, in man, as a potential anorexic, but there is little effect even at 150 milligrams. The 3,4-isomer, 3,4-dimethylamphetamine or xylopropamine, is an adrenergic agent and it has been found to be an analgesic in man at as little as 10 milligrams. This was assayed, rather remarkably, by attaching electrodes to the tooth fillings of the experimental subjects. But with this base, cardiovascular effects were not observed until doses of about 100 milligrams were administered, and toxic effects (nausea and vomiting) were reported at 150 milligrams. There was no suggestion of anything psychedelic.

All three isomers of monomethylamphetamine have also been looked at in man. The ortho- and meta-isomers, 2-methyl- (and 3-methyl-) amphetamine are weak anorexics. At doses of up to 150 milligrams orally, there were signs of stimulation noted—talkativeness and loss of appetite. The para-isomer, 4-methylamphetamine or Aptrol, is more potent. At 75 milligrams (orally, in man) there is clear adrenergic stimulation, and at twice this dosage there are signs of mild toxicity such as salivation, coughing and vomiting.


So my suggestions are:
1) aminopropyl benzocyclobutene
2) aminopropyl benzocyclopropene
(note, the alkene suffix comes from the benzene double bond)

Both much less bulkier than IAP and xylopropamine, my interests goes moslty on the 2nd one since by shape, it's the most similar to amphetamine but the tight carbon bond prevents it from turning into dihydroxyamphetamine (the phenyl becomes a bit distorted in 3d though).
 
3084de5c34.png


This is the very narcotizing levorphanol with one ring decyclicized, which should not decrease it's affinity too much since it is now more flexible. Also I put a phenyl group on there to give it DAT affinity. The N-demethylated form should have more DAT affinity, but probably less opioid affinity.
 
3084de5c34.png


This is the very narcotizing levorphanol with one ring decyclicized, which should not decrease it's affinity too much since it is now more flexible. Also I put a phenyl group on there to give it DAT affinity. The N-demethylated form should have more DAT affinity, but probably less opioid affinity.

What is the point of that thing?

Do you have some data on that compound? Did you have it synthed and bioassay it? Has anyone made it? Do you have some SAR data to justify the posting of that molecule?
 
This one seems interesting.

http://en.wikipedia.org/wiki/LR-5182

220px-LR-5182.png


LR-5182 has two stereoisomers, both of which are active, although one isomer only blocks reuptake of dopamine and noradrenaline, while the other blocks reuptake of serotonin as well.

I'd love to try it.
 
It's interesting in that it's not a phenethylamine, or derived from one, but from a propylamine, some of which are known stimulants (I'm pretty sure the n-propylamine version of MDA has been tested).

I'm willing to bet that this will overlay well with dimethocaine and cocaine. I wonder if diethylamine would be more potent. I bet the answer to that question is known.
 
neat.
receptor affinities for any of them? SAR speculation?
 
I wonder if diethylamine would be more potent.

Or pyrrolidine...

Also would like to see other halogens on the aryl. But this is pointless speculation again, unless someone has made the compounds...
 
98d0b82e76.png

This is ring-opened pethidine. In addition to being an opioid agonist, it should be a much stronger DAT inhibitor than pethidine itself due to flexiblity of the nitrogen position. Somewhat reminiscent of ethylphenidate.
 
GBR-12935_structure.png

Have there been any subjective reports or bioassays of this compound (GBR12935), or similar compounds like other GBRs or amfonelic acid? I know they're commercially available.

The binding affinities are amazing. NET Ki = 277, SERT Ki = 289, DAT Ki = 4.90. I've seen these selective DAT inhibitors before, but never the numbers. Unbelievably potent and selective for dopamine. Cocaine's DAT inhibition is comparitively extremely weak (DAT Ki = 478 ) and extremely nonselective (SERT Ki = 304, NET Ki = 779 ).

I suppose that this compound will have very euphoric almost sedating effects, similar to what some people experience from insufflated methylphenidate, NET Ki = 118, DAT Ki = 90.2 (the lower the Ki the more potent inhibition).
 
Binding affinities have nothing to do with potency by the way.
 
wow...thanks! At my level of knowledge, though, I was wondering more about simple n-propylamine derivatives, particularly homologues of substituted phenethylamines.

I suppose that this compound will have very euphoric almost sedating effects, similar to what some people experience from insufflated methylphenidate, NET Ki = 118, DAT Ki = 90.2 (the lower the Ki the more potent inhibition).

Like methylphenidate? Don't you mean anxiogenic, jittery, and fiendy? ;)
 
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Like methylphenidate? Don't you mean anxiogenic, jittery, and fiendy? ;)

That seems like an exact description of methylphenidate taken orally, but you may find that reviews for snorted, smoked, or IV methylphenidate differ dramatically for the better. To each is own of course. Perhaps the large increase in dopamine required to feel euphoric (and be able to ignore anxiety caused by norepinephrine) is too large to achieve orally. Reasons for this might include slow absorption and the fact that first pass metabolism makes a lot of orally taken methylphenidate inactive due to hepatic cleavage of methyl esters.

Some people claim that more serotonergic drugs are required to remove the anxiety caused by norepinephrine increase. However it seems like a better idea to use more selective DAT inhibitors, which have weak NET and SERT affinities and mainly only dopaminergic effects.
 
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