https://www.thevespiary.org/rhodium/Rhodium/chemistry/iap.html (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?
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.
You are probably talking about Tianeptine: http://www.biopsychiatry.com/tianeptine.htm (http://www.biopsychiatry.com/tianeptine.htm)
However, I suspect it could also enhance the MDMA neurotoxicity if taken together.
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 (http://www.dhushara.com/book/multinet/democ/wed.htm)
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 (http://www.dhushara.com/book/multinet/democ/wed.htm)