Sciencemadness Discussion Board

shulgins rabbit liver enzyme - allylbenzenes to amphetamines?

stoichiometric_steve - 15-2-2007 at 03:44

hi. i hope some of you remember the passage in PIHKAL where shulgin talks about the possibility of converting myristicine to the corresponding amphetamine compound with an enzyme (probably a cytochrome oxidase) from rabbit liver.

does anybody have any further information on this topic? i did what i could, googling, medlining and whatnot, but couldnt find even the original paper.

thanks in advance!

Unch - 15-2-2007 at 08:49

Can we see the passage you're talking about?An exerpt?

In general

roamingnome - 15-2-2007 at 10:11

There probably exists a protein cascade/enzyme that will convert just about anything into just about anything else.

Plants have been doing this quite well and when scientists go for a total synthesis of a plant compound in a lab it can turn into a 14 step lugubrious conundrum. The problem with plants is that they may grow slow or have fickle growth requirements… this is why we don’t have coca plants growing in our closets…hehe

So take for example ma hung, it produces interesting alkaloids right. So I would recommend that you can find out the names of the proteins in general, that perform the operation that you are seeking.

Like reductases or synthases.. Then you can find similar proteins in other organisms that may be more in your next of the woods…
then you wont have to kill rabbits too ;)
Im looking into different synthases that form carbanions, once I found one enzyme I then found more of the same like, 5-Aminolevulinic-acid synthetase from Rhodopseudomonas spheroids. A photo growth bacteria…. Awesome…dude… this may be very easy to concentrate up as compared to the other protein that I found first in a slow growth fungus.. or whatever..


We may understand the techniques of genetic engineering and even almost do some with the right equipment. I mean you can order a phage with promoters built right in these days.,.. its getting quite simple, especially with restriction enzymes….but right now its not really an option… but in the foreseeable future whatever compound you desire will be grown for you simply by adding sugar and water….

So ill stop rambling since I can chat about proteins for ever…

stoichiometric_steve - 17-2-2007 at 05:19

http://www.erowid.org/library/books_online/pihkal/pihkal132....

"This is a material that might be a contributing factor to the pharmacology of nutmeg. The major essential oil from that spice is myristicin, and it is the easiest source of MMDA. It has been reported that the passage of this oil through the liver of a rabbit will generate MMDA in that animal."

how about curing cancer first?

roamingnome - 17-2-2007 at 08:56

A rabbit liver protein can effectively activate the promising anti-cancer drug CPT-11
http://www.stjude.org/media/0,2561,453_5483_3246,00.html

Carboxylesterases metabolize ester, thioester, carbamate, and amide compounds to more soluble acid, alcohol, and amine products

http://cat.inist.fr/?aModele=afficheN&cpsidt=15696079


dont get me wrong shulgins commentary like " at hour 20 i realized my hands" is quite amusing, i saw no mention of proteins in it.

simply typing in "rabbit liver protien" i found the first link then on the second search i typed "Carboxylesterase AND amine"

anyway if i wasnt raised around animal-rites activits i would suggest you get some rabbits and feed them nutmeg, collect their urine, and send a sample to dancesafe.com and see if they test positive. haha

Nicodem - 17-2-2007 at 15:31

Quote:
Originally posted by stoichiometric_steve
http://www.erowid.org/library/books_online/pihkal/pihkal132....

"This is a material that might be a contributing factor to the pharmacology of nutmeg. The major essential oil from that spice is myristicin, and it is the easiest source of MMDA. It has been reported that the passage of this oil through the liver of a rabbit will generate MMDA in that animal."

That used to be a hypothesis to explain the reputed psychoactivity of miristicin and/or elimicin which are contained in the undoubtedly psychoactive nutmeg. This hypothesis got misinterpreted as a theory (unreliable or putative experimental data were misinterpreted for proof of the hypothesis). I have seen the "miristicin/elimicin gets metabolized to MMDA/TMA" or close variations written in scientific books/papers as well, but there was never ever any reference given.
Allylbenzenes do indeed get metabolized by the liver to several derivatives, possibly including also to certain amines, but not into the corresponding amphetamines.
Moreover, as far as I know, it was never scientifically proved that the psychoactive components in the nutmeg are miristicin and/or elimicin while some experiments suggest that miristicin is not psychoactive at all. I think it was only speculated that miristicin and/or elimicin are psychoactive as this would fit so well with the metabolic transformation hypothesis. Unfortunately, Shulgin just helped making this speculation sound even more credible. This is just another example that wishful thinking can be at work in the academic science as well.


Studies of miristicin, elimicin and/or safrole metabolism:

Papers suggesting miristicin is not the (only) psychoactive component of nutmeg:
Quote:
Sherry, Ray and Herron
The pharmacological effects of the ligroin extract of nutmeg (Myristica fragrans).
J. Ethnopharmacol. 6 (1982) 61-66.
A ligroin extract of nutmeg (Myristica fragrans) caused a significant increase in the duration of light and deep sleep in the young chicken. The presence of trimyristin tended to increase the effect of the extract. The extract did not contain detectable amounts of myristicin, elemicin, safrole, or eugenol, which either individually or collectively have been suggested to be the active agent of nutmeg.

Hallström, Thuvander,
Toxicological evaluation of myristicin.
Nat. Toxins, 5 (1997) 186-192.
Myristicin, or methoxysafrole, is the principal aromatic constituent of the volatile oil of nutmeg, the dried ripe seed of Myristica fragrans. Myristicin is also found in several members of the carrot family (Umbelliferae). Several intoxications have been reported after an ingestion of approximately 5 g of nutmeg, corresponding to 1-2 mg myristicin/kg body weight (b.w.). Although these intoxications may be ascribed to the actions of myristicin, it is likely that other components of nutmeg may also be involved. The metabolism of myristicin resembles that of safrole. No information is available, however, concerning the quantitative importance of the different metabolic pathways. The acute toxicity of myristicin appears to be low. No toxic effects were observed in rats administered myristicin perorally at a dose of 10 mg/kg b.w., while 6-7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. A weak DNA-binding capacity has been demonstrated, but there are no indications that myristicin exerts carcinogenic activity in short-term assays using mice. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated to a few mg per person and day in this report, would cause adverse effects in humans. It is, however, at present not possible to make a complete risk assessment, as studies regarding genotoxicity and chronic toxicity, including reproductive toxicity and carcinogenicity, are still lacking.

S.C. Wack - 17-2-2007 at 16:45

Shulgin does give references, but finding the references in the back of his books is an unorganized nightmare. See section 3.2 of
http://www.erowid.org/archive/rhodium/chemistry/shulgin.pea....
for the refs at the bottom of the page.

stoichiometric_steve - 18-2-2007 at 11:06

hmm, okay. seems like it isnt all that easy it sounded like when i first read the comment in pihkal.

i was thinking about making a transgenic plant containing the enzyme responsible for the amination, like cloves or...sassafras ;) just the very prospect of having a plant around with mda in its roots is pretty appealing.

Sergei_Eisenstein - 18-2-2007 at 13:03

Correct me if I'm wrong, but those nutmegheads eating a nut and more don't really act as if they are under the influence of psychedelics. To me, they look rather intoxicated.

Nicodem - 19-2-2007 at 13:18

True. In my experience there is no similarity whatsoever between a nutmeg intoxication and the effects of TMA or psychedelics in general. The nutmeg intoxication is somewhat similar to cannabis, but of lower quality with mostly just the sedative effects. Though it is slightly hallucinogenic, but less so than cannabis, there is absolutely nothing psychedelic at all. The most annoying part is that it lasts for two or three days and the skin color gets a bit grayish. Actually nearly the only enjoying part of the experience is chewing the nutmeg if you like the taste like I do, but some find it nauseating. TMA is something completely different, a true psychedelic and you don't get intoxicated or "stoned" on it. I don't know about MMDA as I have no experience, but in short, there is no way the activity of nutmeg can be attributed to TMA and/or MMDA formed from the metabolic transformation of elimicin and/or myristicin. I would rather expect the active component of nutmeg in its terpene fraction.

roamingnome - 7-9-2007 at 11:03

http://pmr.cuni.cz/Data/files/PragueMedicalReport/PMR%2005-0...

Christmas Gingerbread (Lebkuchen)
and Christmas Cheer – Review
of the Potential Role of Mood Elevating
Amphetamine-like Compounds Formed
in vivo and in furno

Shulgin is on sabatical finisihing a book, so i couldnt submit a question to his anwer page, but then i found this by accident.... this link i feel gives the information you seek....


analogs analogs.... come here analogs...
thats the name of my dog..

S.C. Wack - 7-9-2007 at 14:55

I had read the references since my last post and the way the above paper presents them is of course accurate. Nothing is *actually isolated* or *positively identified*, and I found nothing on rabbits, just rats. They are not worth reading much less uploading.