analgesic tryptamine

[sushitake]

this tryptamine is supposed to have analgesic activity similiar to morphine...I have found relatively little info on it and recieved no responses from suppliers of research chemicals on the availability of the product, any of you bees know anything? about N,N',3-trimethyl-5-hydroxytryptamine? it would seem a good suspect for synthesis for supplying research chemical suppliers no?

[Vitus_Verdegast]

Can you provide a reference for this?

I did a quick search on your compound but came up with nothing, except this paper on analgesic tryptamines:

Substituted 4,7-dihydroindoles.     Remers, William A.; Weiss, Martin J.  (American Cyanamid Co.).    U.S.  (1969),     4 pp.  CODEN: USXXAM 

Patent US3444174

  19690513  Patent  written in English.    Application: US  66-584355  19661005.  CAN 72:66809    AN 1970:66809    CAPLUS 

Patent Family Information

Patent No.   Kind   Date   Application No.      Date 
US   3444174   A   19690513   US   1966-584355   19661005 

Priority Application
US   1966-584355      19661005


Abstract

Substituted 4,7-dihydroindoles were prepd. from the corresponding indoles by treatment with an alkali metal or alk. earth metal in liq. NH3 in the presence of an alc.  For example, a mixt. of 2.4 g 5-methoxytryptamine, 50 ml Et2O, and 500 ml liq.  NH3 was treated with 4 g Li wire.  After 1 hr, MeOH was added until disappearance of the blue color.  Evapn. of NH3 and extn. of the residue gave 1.27 g 4,7-dihydro-5-methoxytryptamine, m. 100-14°.  Other 4,7-dihydroindoles prepd. were 4,7-dihydro-2,7-dimethyl-5-methoxy-N,N-dimethyltryptamine, m. 80-3°; 4,7-dihydro-5-methoxy-N,N-dimethyltryptamine, m. 91-3°; 4,7-dihydro-2,7-dimethyl-5-methoxy-N,N-pentamethyl-enetryptamine; 4,7-dihydro-5-methoxyindole, m. 65-8°; 4,7-dihydro-6-methoxyindole; 4,7-dihydro-5-methoxy-1-methyl-N,-N-dimethyltryptamine; 4,7-dihydro-a-ethyltryptamine, m. 76-9°.  These compds. have analgesic and central nervous system depressant properties. 

[Vitus_Verdegast]

This could also be very interesting:

Synthesis and analgesic activity of N-(N-acetyl-L-amino-acyl)-5-methoxytryptamines.     Dongmei, Han; Chao, Wang; Ming, Zhao; Shiqi, Peng.    College of Pharmaceutical Sciences,  Beijing Medical University,  Beijing,  Peop. Rep. China.   Preparative Biochemistry & Biotechnology  (2000),  30(1),  39-47.  CODEN: PBBIF4  ISSN: 1082-6068.  Journal  written in English.    CAN 132:322109    AN 2000:138442    CAPLUS 

Abstract

5-Methoxytryptamine was acylated with N-acetyl-L-amino acids to give N-(N-acetyl-L-amino acyl)-5-methoxytryptamines which were evaluated for analgesic by the tail flick test.  Among the six compds. that were prepd, the analgesic potencies of N-(N-acetyltryptophanyl)-5-methoxytryptamine and N-(N-acetylglycyl)-5-methoxytryptamine were much more potent than that of melatonin. 

Synthesis and analgesic activity of N,N'-dicarbonyltryptamines.     Dongmei, Han; Chao, Wang; Ming, Zhao; Shiqi, Peng.    College of Pharmaceutical Sciences,  Beijing Medical University,  Beijing,  Peop. Rep. China.    Preparative Biochemistry & Biotechnology  (2000),  30(3),  231-240.  CODEN: PBBIF4  ISSN: 1082-6068.  Journal  written in English.    CAN 133:252248    AN 2000:520139    CAPLUS 

Abstract

5-Methoxytryptamine and L-tryptophan Me ester were acylated with malonic acid, di-Me malonate, or succinic anhydride to produce the corresponding N,N'-dicarbonyltryptamine derivs.  The analgesic activity was evaluated by the tail flick test. All of the compds. exhibited desirable analgesic potency.  This result is consistent with that of N-(N-acetyl-L-tryptophanyl)-5-methoxytryptamine and confirmed that introducing substituted tryptamine into the amide chain of melatonin does enhance analgesic potency.

[Lilienthal]

There can't be anything like "N,N',3-trimethyl-5-hydroxytryptamine". Please check the nomenclature.

[sushitake]

Sorry I didnt include this in the first place. Its in one article titled"future synthetic drugs of abuse"by Donald E Cooper, who I think is a DEA chemist. anyway the article mentions shulgin in the preceding paragraph, in re-reading the paper I realize that this compound may not be researched or mentioned by A.Shulgin. the web address came up as WWW.a1b2c3.com/drugs/desi02b.htm  I have very limited chemical knowledge,so I really couldnt say if this chemical is possible or in existance anywhere. I think this site is a DEA website so some might want to know that before accessing! Tryptophan has some analgesic qualites, as does serotonin, ANd I remember hearing of a tryptamine in either Pihkal or Tihkal that helps opiate withdrawl, and was being sold as an ecstacy rip-off on the street, before being scheduled, both my copies are on loan so I have no page #'s for it. Perhaps this older paperis flawed in some way, or maybe the chemical work was found to be wrong? Its strange that there are no other reports on it on the internet, or maybe it is held by a private source? Any chemists that dispute the possibility of this compound speak up! The mention of the compound is in part 3 of 3 under the analgesic section. thanks for your time as I have asked around on this for awhile now with no luck.

[longimanus]

Sushitake has a little mistake. N,N`,3-trimethyl-5-hydroxytryptamine is not the compound mentioned in the text.
 According to Cooper " There has been discovered one compound which may be of minor interest in that it is an analgesic with potency similar to morphine and can be described as a ring condensation product of N,N`,3-trimethyl-5-hydroxytryptamine (Brossi 1985)."
 I`ve found this article in Erowid, Rhodium and www.a1b2c3.com and the only difference between the three texts is that in the Erowid variant there is "(compound 46, Figure 14)" in front of "(Brossi 1985)".And since there doesn`t exist N,N`,3-trimethyl-5-hydroxytryptamine I`m dying to see Figure 14.

[sushitake]

thanks for the clarification! glad I joined this forum, so its a product of the compound mentioned, and that product is listed in some text by Brossi, but I havnt been able to find the diagrams listed when running searches? Has anyone else?

[Bwiti]

In

Patent US3444174

, example 1, I wonder what would be created if something easier to work with, such as diethylamine, is used in place of the ammonia? Maybe it would have analgesic properties?

[longimanus]

N,N`,3-trimethyl-5-hydroxytryptamine does NOT exist.
 But 1,3-dimethyl-3-(2-methylaminoethyl)-2,3-dihydro-1H-indol-5-ol does.
 And Cooper don`t see any difference!?!

 I searched Medline for the Brossi`s article and found the following:
 
 Further explorations on unnatural alkaloids
 Bossi A.
 J Nat Prod 1985 Nov-Dec 48:878-93
 

Medline (PMID=86142792)

accompanied with the abstract below:

 (+/-)-N1-noreseroline-O-methyl-ether, prepared by a modification of the Julian total synthesis, afforded with R-(+)-methylbenzyl-isocyanate two diasteromeric ureas, converted individually into (+)- and(-)-eseroline after thermolysis, N-methylation and O-demethylation. (+)-Physostygmine was obtained after reaction of (+)-eseroline with methylisocyanate. Biological properties of (-)- and(+)-eseroline and (+)-physostigmine will be reported... continuing with info about colchicine and MPTP research

 What I know about physostigmine is that it`s an agonist of muscarine and respectively - antagonist of atropine. And then I found the information below:

 Physostigmine (eserine),C ₁₅ H ₂₁ N ₃ O ₂ , MW 275.3, CAS 57-47-6, MI 13: 7469, crystaline solid, soluble in chloroform, toxic - forms a carbamylated enzyme complex with acethylcholinesterase that degrades slowly. Crosses blood-brain barrier.


 (-)-Eseroline.fumarate, C ₁₃ H ₁₈ N ₂ O.C ₄ H ₄ O ₄ , MW 218.3 . 116.1, CAS 104015-29-4, white solid, soluble in water or DMSO, slightly soluble in MeOH, metabolite of physostigmine (eserine), potent analgesic.

References:

Medline (PMID=6293841)

Medline (PMID=7092918)

Medline (PMID=2858526)

 So...the analgesic "tryptamine" is actually eseroline. The price of (-)-eseroline fumarate is around 50euro/10mg or 170 euro/50mg and the price of physostigmine is 25euro/100mg (bioresearch grade). Hmm...interesting.

[sushitake]

nice, thanks for the info.So there were some printed errors? if n,n',trimethoxy-hydroxytryptamine doesnt exist why was it listed in this document?I am now going to read up on these substances, thanks agian.

[Lilienthal]

N,N',O-trimetyl-5-hydroxytryptamine would be 5-MeO-DMT.

[longimanus]

Below are some articles about eseroline:

Pharmacology:
  

Medline (PMID=91068238)

it kills brain cells!
  

Medline (PMID=91334549)

  

Medline (PMID=82231462)

  

Medline (PMID=89211823)

  

Medline (PMID=87065740)

  

Medline (PMID=93209316)

  

Medline (PMID=81185784)

  

Medline (PMID=84179927)

  

Medline (PMID=82014213)

  

Medline (PMID=98369748)

  

Medline (PMID=81122677)

  

Medline (PMID=80074451)

Synthesis:
  

Medline (PMID=98296296)

Similar to eseroline:
  

Medline (PMID=92277090)

There is also an article I couldn`t find: `A Formal Synthesis of (+)-Eseroline via an Aza-oxy-Cope Rearrangement` Santos,PF; Almeida,PS; Lobo,AM;Prabhakar,S.; Heterocycles, 2001, 55, 1029-1043.
 

http://www.cpdd.vcu.edu/DEC/acrobat/DEC1997.pdf

would be ineresting for every opiophile.
 
 And, Lilienthal, do you mean the toad, mimosa, etc. 5-MeO-DMT or...cuz I think that "N`" refers to the indole nitrogen?!?

[Lilienthal]

N stands for amine nitrogens, like in N,N'-dimethyl-tryptamine. The indole-N is position 1 and this nitrogen is not an amine.

[sushitake]

im sure you guys noticed that physostigmine can be extracted from the calabar bean. Man this bean is toxic!! nicknamed the "ordeal bean" this plant appears to have been used for murder and torture. I noticed commercial eye-drop preperations of both calabar bean extract and physostigmine for sale on the net. Maybe the metabolite (-)-eseroline is less toxic than physostigmine?.appears to be used for alzhiemers now also.

[longimanus]

So, what does "`" mean?
 "N`" stands for second substituted nitrogen atom. For example N,N`-dimethylehtyleneurea = 1,3-dimethyl-2-imidazolidinone. And which is the second nitrogen in tryptamine? But we are not talking about tryptamine. Look at the structure of eseroline. N,N`,3-trimethyl-5-hydroxytryptamine doesn`t exist. Cooper means 1,3-dimethyl-3-(2-mehtylaminoethyl)-2,3-dihydro-1H-indol-5-ol. As I said - Cooper doesn`t look to be a chemist.
 
 It`s more toxic. Read

Medline (PMID=91068238)

: Eseroline was comparatively more toxic than the parent compound, physostigmine. You can buy eye-drops, hydrolize physostigmine to eseroline and...kill someone slowly. Search for derivates:
 SAR

Medline (PMID=81122677)

 Akuammine

Medline (PMID=92277090)

[Lilienthal]

It just means that both alkyl residues are put on the only free amino positions available - the same nitrogen. It's like a numbering of free amine positions. N,N'-dimethyl-tryptamine or N,N-dimethyl-tryptamine is DMT. Please continue in the Newbee forum   .

[longimanus]

Example:

http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?rxntypeid=30&prep=CV7P0197

. Do you believe them?
 Let`s stop this! The theme of the thread is analgesic tryptamine but we`re arguing about nomenclature.
                                 respectfully, longimanus

[xeno_tropic]

Yes, please do post a ref!