iodoamphetamine

[TrippyZebra]

I've been using 2c-i and love it, I was thinking how an iodine atom on an amphetamine molecule might have an interesting effect but I saw that para-iodoamphetamine is serotonergic but has neurotoxic effects. So what makes fluorine so special with 4-fa and 2-fa? Also could you move the iodine atom somewhere else and it not be neruotoxic? maybe the 2 position? or iodine on other compounds not just amphetamine.

 

[serotonin2A]

Fluorine in 4-FA and 2-FA isn't really "special", but its presence influences the potency and selectivity of interactions with particular proteins in the brain (DAT, NET, SERT, VMAT) in such a way that those drugs produce effects that people find pleasant and/or useful. It isn't the case that the presence of those halogens inherently produces some particular effect.

 

[TrippyZebra]

I always thought Shulgin didnt see much potential in Iodine and a lot of people dislike 2c-i its probably the most underrated 2c imo I think 2c-I-FLY would be interesting.

 

[serotonin2A]

I always thought Shulgin didnt see much potential in Iodine and a lot of people dislike 2c-i its probably the most underrated 2c imo I think 2c-I-FLY would be interesting.

The lack of potential is because adding an iodine to a location makes it a structural dead end. With a methyl group, you can make it longer, branched, or attach other groups.

 

[TrippyZebra]

I'm talking about "potential" for using iodine to make new rc chems like DOI, 25i and 2c-i, iodine adds a unique character to each one of them.

 

[roi]

Well, 2C-I, DOI, 25I-NBOMe, 25I-NBOH, 25I-NBF are a thing already, what more do you want?

 

[serotonin2A]

I'm talking about "potential" for using iodine to make new rc chems like DOI, 25i and 2c-i, iodine adds a unique character to each one of them.

Thats true of any new compounds no matter what group you add to it -- they all have somewhat unique effects. But there is no specific type of effect that can be linked directly to the iodine. In other words, if you find 2C-I especially enjoyable, there is no reason to think that you will find the same enjoyment in DOI or 2C-I-FLY.

 

[blueberries]

I must admit I'm not a fan of 2C-I or DOI for that matter. For me 2C-I was 5 hours of euphoria then 6 hours introspection and a rather nasty comedown similar to C-E's. 2C-E is a godlike compound though so I have no qualms there! I think Iodo amps may be a bit too low in potency due to Iodine's density for it to have a huge impact though, not to mention the cost (which really is why, how and what compounds enter the market).

Overall I think halogenated PEAs are a bit overrated. Sure, 2C-B is a masterpiece and the chloros are nice and stable (a bit like 4-HO-MET, if you see what I mean) but there's nothing too outstanding about it. The only discrepancy here is Fluorine however, as it's applications are endless, Shulgin even related it to "a false hydrogen"! Please don't take this literally though; it certainly isn't. The best PEAs /are/ fluorinated (2C-EF, 2C-TFM, 2C-T-21, 21.5, 22 etc) and the fluorinated amphetamines are a gift from god, they're essentially safe methyl groups (i.e. PMA vs 4-FA). Elsewhere in pharmacology they hold that same weight and it's just fantastic.

Anyway I'm getting off track; IMO we should be exploring more avenues for alkyl groups. Methallyl for instance or even halogens at positions on an alkyl chain (like a chlorine instead of a methyl in an isopropyl group (CH(CH3Cl)). You can get really experimental here and who knows; winners could be around every corner; a golden age for psychedelics (my cup is always half full!).

 

[Solipsis]

Serotonin2a is certainly correct that it is the entire molecule and resultant binding dynamics that make a drug, and the whole "stick a methylenedioxy on anything" mentality, while classic is a very wrong take on SAR.

But, while there are no guarantees or one-on-one characteristics, and while DOX counterparts of 2C-X can have a quite different basis of effects, in some cases it seems moieties in alike chems can carry over a particular effect, at least IME. 2C-C, DOC and 25C all had a relaxation quality that basically no other psychedelic has (possibly because e.g. the chloro enables an affinity for perhaps 2C in a special way, even if the mechanics on 2A are pretty different or the whole binding profile on a whole.

Fluoro's don't necessarily have an effect themselves of course, but they do have the quality of giving a compound a very electronegative group without it being so bulky that it affects binding / effects in adverse ways. It totally matters where you apply this of course! But on positions where this is a perfect solution for the electronic vs steric dilemma, is it any wonder that it can result in some of the best compounds in a certain series?
Doesn't mean that any old position will do for trying to apply a fluoro.

 

[blueberries]

Doesn't mean that any old position will do for trying to apply a fluoro.

It does. That is if it maintains the original group to that position. A single fluorine would probably act as a "safe" methyl as with the x-FA series, resulting in poor psychedelics. You could have 2,5-Di(fluoromethoxy)-4-Bromo-PEA if you wanted, it'd be very powerful though. Shulgin's "false hydrogen" comment (obviously not /every/ situation though!) holds weight, certainly and Traschner's evaluations of Fluorinated psychedelics seemed to confirm it. I wouldn't mind seeing some 5-fluoromethio PEAs ala 5-TOM. Even better; 5-trifluoromethio!

 

[Dresden]

Yes, but the original poster was specifically inquiring about iodo amphetamines, so how does this

or this

look to you?

 

[TrippyZebra]

^^Interesting would this work? What might the effects be?

 

[TrippyZebra]

Thanks for your input blueberries, serotonin2a and Solipsis you guys gave the best answers. I specifically enjoy 2c-i for it's auditory hallucinations (only happens at 30mg+) they are amazing, music sounds like its being preformed live and sound distorts in an interesting way (not an ugly distortion like other psychs.) Ive found that no other 2c gave this effect and figured iodine had something to do with it since i havent experienced this with the other 2c-x's.

 

[Solipsis]

It's worth noting that 3,4-dichloroamphetamine is still neurotoxic like 4-chloroamphetamine, so I'm not inclined to believe the multi iodo amps would be an actual avenue to pursue - though this is just speculation of course.

If compounds like 4-CMC are in a different enough SAR-family from the haloamps meaning that the whole neurotoxicity is not an issue, like vendors claim and I hope for all those users is right (based on what research?) though, choosing those aromatic iodo's on a PEA stimulant molecule that is different enough from producing haloamp like serotonergic activity, then yes iodos are no longer out of grace I guess. Helluva sentence sry

@Blueberries, no sorry have to disagree or you misunderstood me: it certainly does matter where you apply the fluoro approach because it certainly wouldn't work at any position where an electronegative group is anything less than appropriate. Comparing methoxies well I wouldn't know what you yield, but the oxygen bears some negative charge. So no, not 'any position will do', giving an example where you do happen to substitute electronegative groups is not an argument.
But perhaps you were operating under that very assumption, considering only appropriate groups for fluoro substitution thats kind of a truism - so wanted to make clear that the positions where we see those fluoro's are special positions that are important for receptor binding interaction.
For benzos the 2' and 7 positions are important - a d- moiety being known to increase potency - for amphetamines though, it matters that the nonsubstituted amphetamine itself is nicely active, so going from 4- to 3- to 2-fluoroamph not just potency changes twodimensionally, but activity shifts between dopamine and serotonin, mainly.

Returning to iodine, I believe someone recently asked in the 'drawing random molecules thread' about iodo benzos and I do think those are possibilities.

I wonder about 2-iododeschloroketamine and its potency - since not only normal chloro but also the fluoro appears to work fine.

 

[Dresden]

Yes, but if I recall correctly, 3,4-dichloroamphetamine was less toxic than 4-chloroamphetamine, and mescaline is not nearly as neurotoxic as MDA or PMA (mescaline isn't found to be neurotoxic at all, actually), so wouldn't it likely follow that 3,4,5-trichloroamphetamine be expected to be less toxic than both 3,4-dichloroamphetamine and even less neurotoxic still than from 4-chloroamphetamine? (or their iodo analogues, to stay within the query field of this thread)

Also, MDMA and methamphetamine have been found to be neurotoxic, but in practice, I have never noticed any subjective, neurotoxic ill effects on my part, and many people still continue to use both on the global black market to this day. EtOH, which is legal, is also neurotoxic, but look how widespread its use, social acceptability, and availability are!!! If the good aspects of a new drug are found to outweigh the bad aspects for a given user, then some neurotoxicity (especially without clinical manifestation) can be outweighed by the positive aspects of that new drug.

 

[serotonin2A]

People are notoriously bad at detecting many types of neural deficits. An excellent example is hemineglect, which is caused by lesions to the visual system. Patients with hemineglect are often unaware that they completely ignore one side of their body -- for example, they will shave only half of their face or will only put on one leg of their pants when they get dressed.

Long-term methamphetamine users may experience changes in impulse control that they are often unaware of. These are subtle effects, but they can potentially have severe repercussions, especially when combined with stimulant psychosis.

EtOH can have neurotoxic effects but as with any drug it is the dose that matters. Moderate use of EtOH is probably not neurotoxic.

 

[Dresden]

^^Interesting would this work? What might the effects be?

The effects of the top structure, *may* be thought to be similar to mescaline, which has a similar structure; that is the hope anyway.

MESCALINE

However, a published scientific study I read once, found this similar drug only to be a stimulant, not a psychedelic.

^--what the published study was about.

So,1-(3,4,5-trichlorophenyl)-2-aminopropane (SHIVA, to complement the GANESHA of PiHKAL notoriety) might also only be expected to be a stimulant as well; however, I hope it is much more than that.

As for the other one,

it could, according to the published scientific literature to date, reasonably be safe to assume as a MDMA like emphathogenic / stimulant combo drug. Am I right about this last point, science guys? I know that 4-chloroamphetamine can pass for very good, high-dose MDMA, based on a user trip report of Diablo XXX Party Pills, which were known to contain PCA.

SHIVA (my naming)

GANESHA (Shulgin's naming)

(actually, to be rigorously forthcoming it is unclear from reading PiHKAL by Sasha Shulgin whether his invention, GANESHA, was the ethane [PEA] or propane [amphetamine] form of the drug, but according to what else he said there about the series, it can reasonably be assumed that the PEA form of this drug is equally or very nearly equally as potent as the amphetamine version).

PCA

Whether all these new drugs have a chloro or an iodo should only make for minor qualitative differences between and among these drugs; thus, you asked about the iodo forms, but I answered using the chloro forms. They are practically interchangeable, as halogens, as far as answering this question is concerned anyway.

Finally, to possibly further indemnify the belief in anyone that this post may be at least somewhat germane to the comings and goings of the black market, street drug world which most of us BL users find ourselves subservient to in that we depend on its wares as often as 1x per day, on March of this year, 2016, in Vienna, Austria, a pressed pill was found to contain this ring halogenated methamphetamine, according to ecstasydata.org:

PCMA

And yet, no apparent PMA/PMMA type overdose deaths among ecstasy pill poppers was noted there recently, to my knowledge. A good thing about the halogenated amphetamines, other than apparently qualitatively substituting for MDMA, is that their synthesis does not depend completely on the obtainment of the very hard to get, very watched, very hard to make from scratch,

SAFROLE

the heavenly smelling chemical whose absence of which made widespread, available street MDMA an impossibility for a good decade in the early 2000s and still does in everywhere in the world but the clandestine labs of Europe, whose chemists have discovered another, commercially available and unnamed by me precusor for their Teslas, Dominos, Bugattis, and whatnot high dosed pressed MDMA pills.

 

[LearntYoung]

All fun and games, but if you ask me, the lack of interacting energy between those iodo substitutes and their neighboring atoms would cause the molecule to become unstable. The lack of elektro negativity, that becomes greater when moving from Fluorine down to Iodine increasingly weakens the bond between the drug and its 'halogenation.' I think the reason for the p-Chloro substitute to show destructive properties towards serotonin receptors, whereas the p-Fluoro substitution is merely an adaptation of the properties that amphetamine is already showing, is caused by the lack of strength in the Chloro bonding. Of course this is speculation, but well... 8(

 

[adder]

Well, I see no reason why any 3,4,5-trihalophenethylamine might resemble mescaline, chlorine is a poor hydrogen bond acceptor and bromine and iodine don't act as such at all, that's the job those methoxy groups do in 2C-X's and mescaline analogues. At least one of them seems crucial for any psychedelic activity. So if one desperately wanted to stick iodine on something and wanted that something to be a psychedelic, I suppose 4-iodo-3-methoxyamphetamine may be a viable and possibly non-neurotoxic option akin to 4-methyl-3-methoxyamphetamine.

I think the reason for the p-Chloro substitute to show destructive properties towards serotonin receptors, whereas the p-Fluoro substitution is merely an adaptation of the properties that amphetamine is already showing, is caused by the lack of strength in the Chloro bonding. Of course this is speculation, but well...

I'm not sure if I understand what you mean. Do you mean the aromatic C-Cl bond being weaker than C-F? In my opinion that's the least important thing here. p-iodoamphetamine is less neurotoxic than p-choroamphetamine, so how would you explain this discrepancy? All halo groups withdraw electron density from the aromatic ring, so clearly that's not where the difference is. I suppose it all comes down to halo group size and C-X bond polarization and the partial charges it creates. p-methylamphetamine doesn't seem to be neurotoxic and methyl group is similar in size to chloro group, bromo and iodo are considerably bigger and their C-X bonds are less polarized.

 

[Dresden]

Based on what I've read about

p-METHYLAMPHETAMINE aka 4-METHYLAMPHETAMINE,

it's a nightmare drug with terrible side effects, such as an extreme increase in suicidal behavior, which makes me even more leery of the way that the term "neurotoxic" is bandied about as not appyling to certain drugs with terrible mental side effects but is applied to others which are seemingly benign.

As for your 3,4,5-halogenated amphetamine comment, neither one of us knows if they will substitute for mescaline or not (though we both have our hypotheses about it, though mine is tentative I would say), but it does makes me wonder: Does 3,4-dichloro(meth)amphetamine substitute for MDA or MDMA?