Indanylamphetamine - A new potent MDMA analog

[Rhodium]

https://www.thevespiary.org/rhodium/Rhodium/chemistry/iap.html

Are there any pioneers out there who wants to try out a new potent MDMA analog?

[obituary]

wouldn't mind running the procedure- but new products are always on the shit list until approved by many other bees.  unless of course, you're sending free samples

[Rhodium]

Someone has to be the first to do it, if everybody thought like you, there would be no innovation in the field. And since it has been proven that it hit the streets in Australia, it must be interesting enough for trying out, and the animal test also look favorable. I haven't tested it, because I lack the lab needed to perform the reaction myself. If I had, I would most definitely try it out.

[yellium]

MMA is also interesting. Do you know if anybody has tasted it?

[Rhodium]

No personal accounts, but there have been seizures of pills contaning MMA in Italy...

[obituary]

sorry, although obit is interested in the field- obit is not willing to risk life and limb for it.  once it has been consumed and the risks fairly established (as well as one can) then it's another story.

[Quicksilver]

I always get excited when these type posts come up, but innovation always seems so slow.
Remember this one:

Post 185131 (missing)

(hest: "New Amph.  more potent than LSD", Serious Chemistry)
A blitz of activity...then nada.       Don't mind me while I go mope.

[methwerx]

I am in Oz, I have held this stuff in my hand, but not tried it. Its been out for atleast 3 years. The indanyl ring is not as activating as the methylene dioxy ring, infact its darn deactivating. This makes access of indan difficult. But the compound is 6 times as potent and lasts 3 times as long as its md cousin!! Someone get this one going, it has been highly recommended! A friedel crafts alkylation had 7% yield, and shulgins aldehydation had 15% yield. Its a bitch. But worth a try....


tip of the month: slugs in your bathroom keep the mould of the grout.

[Rhodium]

Are those yield figures from personal experiments, or do you have references for the reactions? What is your source for the duration figure? Do you have any qualitative reports of the experience of the action of the compound?

[yellium]

from rhodium's site:

IAP is also one of the most active serotonin-releasing agents known so far

Which probably means that it will be very euphoric the first time. But after that? Instant depression?

(5-HTP or tryptophan may be a solution to that, but both taking indanylamphetamine and a tryptophan rich diet downregulate 5-ht receptors, at least temporarily.)

See for example Pharmacopsychiatry 34: (4) 147-149 JUL 2001.

Effect of a low tryptophan diet on the prolactin responses to the 5-HT2A agonist DOI in the rat

Low tryptophan (TRP) diets decrease brain serotonin (5-HT) content and produce an up-regulation of the function of some but not all 5-HT receptor subtypes. The aim of the present study was to assess the effect of a two week low TRP containing diet on the plasma prolactin(PRL) response to the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) in the rat. The low TRP diet significantly reduced plasma total TRIP as well as brain 5-HT for the two weeks of the study although plasma free TRIP was ecreased only for the first week of the diet. The PRL response to DOI was significantly increased in the first week of the diet but returned to normal in the second. The results suggest that a low TRP diet produce a transient up-regulation of brain 5-HT2A receptors.

[methwerx]

sorry Rhodium, I cant say anymore.....
tip of the month: slugs in your bathroom keep the mould of the grout.

[Rhodium]

It doesn't mean it releases a larger amount of serotonin than MDMA and friends, just that it is the one compound needing the smallest dose (in micromoles/kg bodyweight) to achieve the same release. I have tried the about equipotent serotonin-releaser 4-MTA once (2x125mg in one night) and was not feeling depressed the day after. Actually, I was a lot more vigilant than after MDMA.

[yellium]

What I was trying to say was that frequent usage of IAP will have similar effects as MDMA, apart from the neurotoxic effects. Weekly usage will give the same 5-ht depletion, and I guess that tolerance develops in a similar way as for MDMA. 

[Rhodium]

Yes of course. One cannot have the serotonin trip without having a measured serotonin low afterwards (unless a really novel pharmaceutical tool is invented, like a enhancer for fast serotonin buildup and release).

[psycosmo]

I wonder what would happen of the oxygens in the MDO group were replaced with nitrogens (esp. w/ an O inbetween), or sulphers.....
so many potential drugs, so little time

[Rhodium]

With nitrogens, the material will become too polar to cross the BBB, and thus be inactive. Sulfur atoms would be a GREAT idea, but if you do a search on compounds like that, the literature is VERY scarce (a dozen mentions in the entire CA on methylenedithiophenyl cpds). Those compounds seems to be VERY hard to synthesize.

[goiterjoe]

I was reading somewhere about there being a german pharmaceutical used to treat depression that was a selective serotonin reuptake accelerator(not inhibitor) that also made the brain produce excess serotonin.  sounds like this pill would be a lot of fun to take with psychadelcics.
Sed quis custodiet ipsos custodes?

[Rhodium]

You are probably talking about Tianeptine:

http://www.biopsychiatry.com/tianeptine.htm

However, I suspect it could also enhance the MDMA neurotoxicity if taken together.

[PrimoPyro]

What would cause that? Would the standard antioxidants, etc prevent it? (Do you think) But why increased neurotoxicity?
Of COURSE we don't know what we're doing! That's why it's called research! Member: C_F Fan Club

[Rhodium]

The neurotoxicity is caused by dopamine being taken up by the serotonin reuptake channel, where it is oxidized to compounds which are or creates free radicals, which causes the damage. Serotonin reuptake blockers (SSRI's like Prozac) taken a few hours into the MDMA "trip" prevents the dopamine being taken up by this channel, thus preventing neurotoxicity. A reuptake enhancer would cause more dopamine entering, and potentially causing more damage.

Yes, large doses of antioxidants may very well prevent this, but I wouldn't take the chance myself though, that that would be enough. YMMV.

[ChemisTris]

psycosmo said: "I wonder what would happen of the oxygens in the MDO group were replaced with nitrogens"

I have thought about this too. Although Rhodium said it may be too polar to cross the blood-brain-barrier, and thus be inactive, i have found a referance that would suggest some potential activiy.

Medicinal agents in the series of b-phenylisopropylamine derivatives.  VI.  Benzimidazole analogs of b-phenylisopropylamine.
Piotrovskii, L. B.; Kudryashova, N. I.; Khromov-Borisov, N. V.    Inst. Eksp. Med.,  Leningrad,  USSR.
Khim.-Farm. Zh.  (1975),  9(10),  3-5.  (CA 84:30964)

Abstract
Aminopropylbenzimidazole (I, R = H) was obtained in 50% yield in 6 steps from p-O2NC6H4CH2CHMeNH2 by redn., acetylation, nitration, deacetylation, redn., and cyclization by HCO2H.  Addnl. obtained was 60% I (R = Me).  I have potential sedative activity (no data).
(my bold)

The journal is written in Russian. I don't have access to this, nor do i speak Russian, so if any Russian speaking bees are interested in this, i would love to hear more  

My next thought is the potential placement of a lipophilic group on one of the benzimidazole nitrogens. Not a bulky lipophilic group, but something small, Me or Et to make the molecule more suitable for crossing the BBB, but then the question is - will the molecule have suitable activity at the receptor.

Would anybee care to comment?
Got democracy?

http://www.dhushara.com/book/multinet/democ/wed.htm

[Rhodium]

VERY interesting... I would love someone to prove my assumption wrong about nitrogen-substituted derivatives being too polar to be active, because if that is true we have a lot of nitrogen-based analogs to try out...

[ChemisTris]

Yes, Rhodium, it would be most interesting! I originally became interested in these analogues after learning more about isosteres. I had assumed that they would posses some activity, but we really need details now.

Of the (limited) liturature i have about benzimidazole analogs, much of it is based around Dopa analogues with carboxylic acid groups, and obviously these are too polar to cross the BBB.

There is a ref where X (where X = the methylene bridge) has been replaced by C=O (this would be too polar i assume), N (again more polar), SO₂ (polar again). These are of limited value to us, but how about where X = C-Me. (all these with the N-X-N ring system). The C-Me has been prepared, but on a molecule with a COOH on it   .
The referance for all this was:
Synthesis of dopa and dopamine analogs with acidic imido-functionalities in heterocyclic ring moieties instead of the phenolic hydroxyl groups.
Schmidhammer, H.; Hohenlohe-Oehringen, K.
Inst. Organ. Pharm. Chem.,  Univ. Innsbruck,  Innsbruck,  Austria.    Sci. Pharm.  (1983),  51(1),  8-16. CA 99:140318

The abstract i have of this doesn't say much except that the were prepared through known methods.
Got democracy?

http://www.dhushara.com/book/multinet/democ/wed.htm

[Lilienthal]

The -O-CH(CH3)-O- analogs are inactive. That has been published several years ago in J. Med. Chem.

[Dr_Heckyll]

There are always surprises. The other day I ran into some compounds which had a quarternary nitrogen and still were antidepressants, i.e. get through the BBB. I wouldn't have believed it if I hadn't seen the pharmacological data with my own eyes. This is so contrary to all I would have expected. And they were active orally! In a way that was a mind-opening experience for me! I ain't say again: oh, this is too polar   ...


For every molecule there is a moron thinking it will be a great drug

[tiresias3]

Nitro groups have a plus charge on the N and may be too polar to cross the BBB, but cyclized alkenylamines attached to a phenyl such as indole are certainly not too polar to cross the BBB. 

However, these PEA's are 'Thanatos' in nature because their N (an aniline) is antiaromatic, rather than 'Eros' like the alkoxy-AMPs, with their activated phenols and such.

DMT is 'Thanatos.' 

5-carboxaldehyde-indole is a new product from Sigma-Aldrich @ $85.15 per 5 grams.  You may or may not bee interested,
"I mean, we'll take it slow, I really don't know."--Tricky

Note:  Regular indole is 3-carboxaldehyde-indole, unless I'm naming it wrong, but I think you will at least get the idea.

.

"You're schemin' on a thing that's a mirage.  I'm tryin' to tell ya'll now it's a sabotage"--the BBB's, _Ill Communication_

[Rhodium]

I get the idea. There have already been something published about 4-(N,N-dimethylethylamino)-indole compunds (they called them "iso-DMT's") and they were active, at least in in vitro assays. Very cumbersome synth though. Now, could you carry the above 5-indolecarboxaldehyde through all the usual steps without anything attaching to the very reactive indole 3-position?

[moo]

Oh, yes   . From Tihkal #48, alpha-methyltryptamine, extensions and commentary section:

"And there are five possible chain relocation, from the normal 3-position to the 2, the 4, the 5, the 6 or the 7-positions. All five "alpha-methyltryptamine" isomers are known, but only one is known to be active in man as a CNS active material. This is the 5-isomer, 5-(2-aminopropyl)indole or 5-IT, which, at 20 milligrams orally, is a long-lived stimulant producing increased heart-rate, anorexia, diuresis, and slight hyperthermia for about twelve hours."

[TheRampartLion11]

The IUPAC name for that compound is actually IAN-AMP, but who knew?

.

[gamilaraay]

[Promethium]

There is the possibility that you obtained a mixture of 4- and 5-indanylamphetamine (2-indan-4-yl-1-methyl-ethylamine and 2-indan-5-yl-1-methyl-ethylamine). J. Org. Chem., Vol. 39, No. 19, 1974, 2852 describes a procedure very similar to yours and it produced a 20:80 mix of 4- and 5-indanaldehyde. A different temperature or whatever...and your mix might have been even more unfavourable. The 4-IAP might have then modified the psychopharmacology of the 5-IAP, who knows?

I wonder, btw, why those who have apparently tried IAP (Rhodium, FractalFlower...) are not sharing their experience. Is IAP the great big secret? Basic pharmacological considerations indicate that it's some 4-6x more potent than MDMA, with a significantly longer duration of action due to the absence of the metabolically unstable methylenedioxy group.

PS: According to your write-up you used TiCl4 as catalyst, just like in the JOC paper, where it leads to the 20:80 mix, while Nichols in his JMC publication used SnCl4 and got a 98% yield. You could check the melting point of your final product, which should be 218-219 °C.