• N&PD Moderators: Skorpio | someguyontheinternet

acacia rigidula - natural amphetamines??

The authors didn't even respond to Shulgin as far as I know... Phytochemistry isn't a terrible journal as far as plant biochemistry is concerned, but as far as I know the logical biochemical pathway to methamphetamine or amphetamine in a plant would be through cathinone or methcathinone. The whole thing is very suspect, and I'm pretty certain it can be chalked up to contamination.

A similar study about benzodiazepines in potatoes is here: http://www.sciencedirect.com/science/article/pii/0006295289900919

Detection of desmethyldiazepam and diazepam in brain of different species and plants
Elisabeth Unseld, Devarakonda Rama Krishna, Christine Fischer, Ulrich Klotz


Purchase
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, D-7000 Stuttgart, Federal Republic of Germany
Received 2 November 1988; Accepted 30 January 1989. Available online 5 November 2002.

Abstract
Recent data suggest that desmethyldiazepam (DD), a major metabolite of several benzodiazepines (BZD), might be of natural origin. Therefore we tried to quantify DD and diazepam (D) in animals during maturation (e.g. hen, chicken, eggs), in brain of species at different evolutionary stages e.g. salmon, frog, monitor/reptile, rat, cat, dog, deer, bovine) including newborn and adult humans. Since low concentrations of DD (range 0.01–0.04 ng/g wet wt) and D (range 0.005–0.02 ng/g) could be measured in different species by sensitive and specific mass spectrometry (GC-MS), we analysed also several plants (e.g. maize corn, lentils, potatoes, soybeans, rice, mushrooms). Again, DD and D could be detected in low amounts (0.005–0.05 ng/g) in some plant products. This would suggest that DD and D might be of natural origin and incorporated via the foodchain into the animal and human body. The biological role or clinical relevance of these intriguing findings need still to be elucidated.

It always seemed weird to me that the authors would believe this not to be from groundwater contamination but from the potatoes themselves, since I think it's pretty unlikely potatoes and other plants would naturally incorporate a chlorinated aromatic ring.

There was a pretty big article in Nature the other year where they were able to get a plant to produce unnatural chlorinated byproducts by genetic manipulation, but as far as I know halogenation of organic compounds with chlorine or bromine is extremely rare in the biochemistry of non-algal multicellular eukaryotes.

http://www.nature.com/nature/journal/v468/n7322/full/nature09524.html

http://pubs.acs.org/doi/abs/10.1021/ar9701777
 
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this thread was started in 2006 and its 2012 now. are you guys really that slow working to fix such interesting puzzles or just too drugged up to care ? seriously, this should be continued until one of you fucking confirms acacia is reliable source of any mentioned molecules.
 
this thread was started in 2006 and its 2012 now. are you guys really that slow working to fix such interesting puzzles or just too drugged up to care ? seriously, this should be continued until one of you fucking confirms acacia is reliable source of any mentioned molecules.

I think that it's simple very likely contamination in the lab. not a particularly interesting puzzle.
...
Why are you angry specifically at posters in ADD? Not all of us are researchers in biochemistry with specialization in ethnobotany. :P

ebola
 
It has been rumored that a rare plant (growing only the northeast slopes of mount Azerbaijan ) was found to contain methadone.
 
Would be funny that one of the fews part of the world where you can't get treatment with methadone were to be found a plant that produces it.
I think no plant will produce such that kind of compound, more chemically similar to a dissociative than an opiate.

And about the acacia and the alpha-metil-PEA's in plant... not without a ketone or an hidroxyl. So far... and I find more real Shulgin than the other paper that no one stands for it...
 
Quite logically, methadone is naturally occurring, because it was created by a naturally occurring animal (man). But I digress....
 
I have talked to one of the authors. She seemed to think that contamination was unlikely. I'm pretty sure I have her response saved. I don't think I'd delete that. I'm pretty sure I showed it to a few people on here as well.

Why Shulgin had no response and I did right away? I used email... ;)
 
and I find more real Shulgin than the other paper that no one stands for it...

As far as I'm aware, Shulgin never analyzed the plant.

And as far as I'm concerned, until someone else looks at it, there's no reason to doubt the authors. It came from a reputable university, in a reputable journal, and so far as I can tell, none of the authors are currently involved in the marketing of "supplements" containing the plant or synthetic compounds that were "found" in it (that was suggested to me by a few people, actually, but I couldn't find any evidence of it, and it seems faintly ridiculous).
 
It's the last author who is typically the principal investigator for biology papers (there is some variation for some fields). If it is not true then this guy is publishing stuff for his career. If it is true, it is an incredibly discovery but not totally unexpected. The reason for this is that ANY ligand you discover that binds to proteins in the human can potentially bind to related proteins in other organisms (and vice versa). In my experience, looking at thousands of proteins and their active/binding sites, protein structure is highly conserved (this is a well know fact) and protein ligand pockets seem to be even more conserved. In other words, nature's using the same shapes with different chemistry.

This is because of evolution. All our drug discovery, including the discovery of novel drugs, is based on what works in human. So we could think we're creating a "novel" compound but if it fits in the pocket, then the likelihood that it resembles another metabolite that binds to the protein from which it evolved. Drug discovery has been based on exploiting plant metabolites and most drugs we use (I'm referring to prescription drugs ) have a plant source. So this is like a reversal.

One way to verify this is to see what proteins it binds to in the plants. If those proteins appear to contain similar binding sites to what we know in human proteins that these compounds bind to, then we can be more confident this is significant.

Interestingly enough, there's a study going on to do this in a top down manner. Meaning that someone's comparing all plant metabolite binding sites (for 1000 plants whose transcriptomes aren't public yet but you can google this project) computationally to all drug targets (both the global fold and the binding site). The logic is that if there's a similarity to binding sites (there will be some), then those metabolites that could fit in the site could be potential drugs or drug leads.


Various species of acacia are found around these parts. I'm constantly digging up wattles that pop up around the house - and we don't even live in the country!

If you read Shulgins page on this, he sounds a little skeptical, as he made attempts to contact the authors, but to no avail.

Acacias and natural amphetamines


Here's abstacts of the two mentioned papers. Note Clement co-authored both.
 
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If it was contamination, I'd want to know the source. What contaminant could have all those? I don't think contamination is the answer.

I am skeptical though about the discovery. If we had the plant genome we could look for proteins similar to ones that we know amphetamines bind to. :/ That's what it'd take to convince me if it came from that group.

The group could've made a honest mistake. Or...


I have talked to one of the authors. She seemed to think that contamination was unlikely. I'm pretty sure I have her response saved. I don't think I'd delete that. I'm pretty sure I showed it to a few people on here as well.

Why Shulgin had no response and I did right away? I used email... ;)
 
So Acacia leaf is what is people chew with betel nuts?

Hmm, interesting.

One question is whether it is possible. I think it is from a theoretical point of view. Each of the individual compounds is possible due to evolution in different plants. That one plant would concentrate them all (almost like collect them) and contain all the pathways to make all these compounds is possible but unlikely.

There is the other intriguing possibility that Acacia was the ANCESTRAL plant for all these alkaloids in nature and it was OTHER organisms that took what they could from this plan. Let's assume the paper is valid and that the GC/MS data is interpreted honestly. What could've happened? Are they collecting the plants from about the same site? Could there soil contamination from the Shulgin lab to here? (:

I'm willing to believe it enough to suggest that the genomes of these plants should be sequenced. If they contain all these compounds, they could have OTHER metabolites that could be really useful as therapeutics.

Why would you say that? Plants can do amazing things. Acacia contains both nicotine and DMT, after all.

Anyways, as for the amphetamines, all I can say is that Acacia is used in preperation of betel quids, which are a stimulating drug, and various species are used for aphrodisiacs.

Acacia baileyana contains B-phenethylamines.
 
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