Sinomenine

[SynthMorph]

Sinomenine is an alkaloid found in the root of the climbing plant Sinomenium acutum (http://en.wikipedia.org/w/index.php?title=Sinomenium_acutum&action=edit&redlink=1) which is native to Japan and China. It is traditionally used in herbal remedies in these countries, as a treatment for rheumatism and arthritis. This stuff is a morphinan derivative and is related to levorphanol and dextromethorphan. I was reading this stuff activates the mu opiate receptor and has some antagonistic effects and eliminates the morphine withdrawal symptoms. Apparently this stuff is totally available and legal. My guess is it'll become the next thing for opiate detox or maintenance therapy. Check out the molecule:

http://upload.wikimedia.org/wikipedia/en/c/c4/Sinomenine.png (http://upload.wikimedia.org/wikipedia/en/c/c4/Sinomenine.png)

[WarmCyanide]

i can't figure out that molecule but i trust you. it looks like its on its way up. i like the hash marks.

[SynthMorph]

My interest would be how do I turn that ^ into something better?

[Saint]

Sounds interesting.. I'm going to google a bit myself.

And sinomenine-maintenance sounds way better than pufferfishmaintenance as well..

[SynthMorph]

Pufferfishmaintenance, that's hilarious. My friend used to have one and called it Jabba the Hut.

[Saint]

Pufferfishmaintenance, that's hilarious. My friend used to have one and called it Jabba the Hut.

Seriously, there was a thread about pufferfish not too long ago, supposedly helps with wd-s..
Can't really picture it though.

[SynthMorph]

Yeah, those toxins in small doses can kill pain. I read they can also cause hallucinations and make you crazy. Wouldn't mind eating one, apparently they're hard to prepare.

[Consumed.]

Yeah, those toxins in small doses can kill pain. I read they can also cause hallucinations and make you crazy. Wouldn't mind eating one, apparently they're hard to prepare.

When I was younger of friend of minds grandmother cooked pufferfish a lot. It tastes almost exactly like flounder. Real light fluffy texture. She prepared about the same way too; frying pan with butter. The family was 100% hardcore Italian too, not Japanese. Im not sure but i think there's a poisonless kind too.

[SynthMorph]

Sounds good, I love fish, sushi all that. I went down south once to Ohio in a jazz bar and had the best meal ever; fried catfish. I know it sounds weird but once you try it you'll know what I'm talking about.

[Saint]

Sounds good, I love fish, sushi all that. I went down south once to Ohio in a jazz bar and had the best meal ever; fried catfish. I know it sounds weird but once you try it you'll know what I'm talking about.

Mm, fish. In Panama I used to eat red snapper fried in coconut oil, some salad and fried cassave on the side..

[norseman]

Seriously, there was a thread about pufferfish not too long ago, supposedly helps with wd-s..
Can't really picture it though.

I started that thread, still yet to try it out, not sure if I would even give it a try, but this "Sinomenine maintainence" sounds really interesting.

Did anyone else notice that Saint and Synthmorph both have cats for avatars, and they were both just talking about eating fish???????? cats & fish?????? hmmmm; something odd with those two philes. hehehe

[rockbottom]

all the good shit comes from plants from opiates to psychedelics---i just tried salvia and it kicked my ass--so why not? the chinese really know their shit

[Saint]

I started that thread, still yet to try it out, not sure if I would even give it a try, but this "Sinomenine maintainence" sounds really interesting.

Did anyone else notice that Saint and Synthmorph both have cats for avatars, and they were both just talking about eating fish???????? cats & fish?????? hmmmm; something odd with those two philes. hehehe

... you don't wanna know...

[Hammilton]

I'm afraid that this won't work for maintenance. It's the wrong isomer- it doesn't seem to bind to the mu receptor at all, and all of it's analgesic effects are due to side actions.

It's a dextro, you want the levo isomer (i doubt it'll be very potent, though), but it doesn't seem to have been assayed as a NMDA antagonist. It may have some positive effects there.

very interesting that this is a plant molecule. Just need that isomer fairy, I guess.

[jacky]

yes, this compound has some potential I think, but not as something to be used recreationally.

I think there is some question of metabolite production with this compound as well, endogenous catabolic/metabolic processes could produce active metabolites/catabolites.

I wasnt aware of its comparison to methodone/levo.
interesting.
thanks for the information.

this compound and related isoquinolines are found in a variety of plants, there may be some prolific natural sources for this compound.
anytime the chinese use the product, you can pretty well rely that at least the raw material is going to be avialable.
now, I know that this compound is avialable 98% pure, and should be as legal to source as menthol or camphor crystals.

warning of antagonist activity is pretty important.

when I obtained pure matrine and tried a reasonable but high dose of the pure compound, I felt like CRAP for 2 hours.
but when I took herbs with matrine in them, like chinese medicinal sophora products (not the southwestern sophora bean!!), I feel a nice addition to my other herb regimines.
and it turns out that matrine might not even have classic opioid activity afterall, the data is debated/contradindicated.

I think the compound does have potential for analog study.
and I know that it has its effective uses for medicinal therapy.

and the human body can do some wonderful things with compounds in its factory of life productions.

it would be great if someone could produce a nice mu active compound with this one. the cost of precursor material would be relatively cheap if its harvestable similiar to other compounds isolated by the natural products industry.

[bigNasty]

I went down south once to Ohio in a jazz bar and had the best meal ever; fried catfish.
I know this is an old thread SM but i thought this was funny.

Down south all the way to...................OHIO! LOL. You probably meant you went south to Ohio.

The words "down south" to we southerners means below the Mason Dixon Line. I don't consider Ohio down south at all, thats way up north!!

Peace and chicken grease ya'll, while spitting my tobacco spit in a tin bucket

[jacky]

heres something interesting I found-


"Activation of opioid mu-receptor by sinomenine in cell and mice.

Wang MH (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Wang%20MH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Chang CK (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Chang%20CK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Cheng JH (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Cheng%20JH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Wu HT (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Wu%20HT%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Li YX (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Li%20YX%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Cheng JT (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Cheng%20JT%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Department of Anesthesiology, En-Chu-Kon Hospital, Sanxia Town, Taipei County, Taiwan.
Sinomenine, one of the alkaloids extracted from roots or stems of Sinomenium acutum, is documented to show antinociceptive action but the action mechanism is still unclear. The present study was aimed to investigate the effect of sinomenine on opioid mu-receptor (OMR). In Chinese Hamster Ovary (CHO) cell transfected with OMR, the binding of [(3)H]naloxone was displaced by sinomenine in a concentration-dependent manner. This compound also raised the phosphorylation of OMR in these cells. In a tail-flick test, sinomenine produced dose-dependent antinociception in mice, which was dose-dependently inhibited by pretreatment of naloxonazine, a selective OMR antagonist. Long-term pretreatment with sinomenine may delay the analgesic tolerance of morphine. The obtained results suggest that sinomenine has an ability to activate OMR, implicating the potential of sinomenine to be applied in clinic.
PMID: 18692550 [PubMed - in process]"




and then there is this report, which makes me wonder, can this compound slow the release of endogenous peptides like our opioid peptides, from leaving our body? the result if yes, is that the compound could lower opiate tolerance, even if its endogenous opiates?


"itre du document / Document title

Effect of sinomenine on human cytochrome P450 activityAuteur(s) / Author(s)

YAO Yong-Mei ; WEI CAO ; CAO Ya-Jie ; CHENG Ze-Neng ; OU-YANG Dong-Sheng ; LIU Zhao-Qian ; ZHOU Hong-Hao ; Résumé / Abstract

Background: Cytochrome P450s superfamily expressed widely in organisms are known to play an important role in the biotransformation of many endogenous and exogenous substances. Inhibition or induction of cytochrome P450 isozymes is one of the major causes for clinical drug-drug interactions. Sinomenine can be metabolized to at least 2 metabolites in human, rat in vivo and in human liver microsomes. The major metabolite was identified to be N-demethylsinomenine. However, which CYP450 isozymes mediated by sinomenine in vivo and in vitro is not known. Method: In vitro study, 6 probe drugs were incubated with or without sinomenine respectively to study the effect of sinomenine on different cytochrome P450s activities in human microsomes. In vivo study, a 5-drug cocktail approach was used to study the inhibitive and inducing effect of sinomenine at normal clinical dose on cytochrome P450s activities. Results: Sinomenine (50 (μmol/1) had no significant effects on the activities of CYP1A2, CYP3A4, CYP2C9, CYP2E1, and CYP2D6, but it decreased the activity of CYP2C19 by 69% (p=0.012) in human microsomes. In vivo, sinomenine showed almost no significant effects on the activities of CYP1A2, CYP3A4, CYP2E1, and CYP2D6, but enhanced the elimination of mephenytoin by 73% (p=0.032). Conclusion: Sinomenine (50 μmol/1) inhibited the activity of CYP2C19 in human microsomes, but in vivo sinomenine at normal clinical dose enhanced the elimination of mephenytoin.Revue / Journal Title

Clinica chimica acta ISSN 0009-8981 CODEN CCATAR "



I am glad you pulled my attention to this compound.
I had some real interest in it a year or so ago, and researched a little about it. now seeing more data on the compound makes me realize that something like this has important potential in my book.
I was at first interest in it while researching reticuline and salutaridine isoquinoline compounds, sinomenine if I am not mistaken is somewhat similiar, and might be implicated in the precursor line up between isoquinoline and morphine.
things get confusing when you are just a lay-opiophile, and not an expert, so I may have dropped the ball with a few thoughts, but this much is sure, this compound deserves a thorough going over by bioassay by opiate tolerant and not opiate tolerant individuals, hell, its important even for non and + OPIOID tolerant individuals.

getting the pure compound probably is easy, but maybe not in amounts under a 100 grams, or for that matter, a kilo...
but, obtaining the compound in the medicinal plant it occurs in is going to be easy, and probably cheap. plus, here is always the possibility that this plant contains other similiar compounds with more favorable effects.
similiar to THP and corydalis, or matrine and sophora subprostata, sinomenine might be better worked with in the full spectrum organic condition of the raw plant material.

I am getting some!
I might add this to my new mixture of chinese medicinals supposed to help opiate withdrawl.
replace the aconite with this plant, just for research purposes.

thanks again for the nudge.

[robojunkie]

I'm afraid that this won't work for maintenance. It's the wrong isomer- it doesn't seem to bind to the mu receptor at all, and all of it's analgesic effects are due to side actions.

It's a dextro, you want the levo isomer (i doubt it'll be very potent, though), but it doesn't seem to have been assayed as a NMDA antagonist. It may have some positive effects there.

very interesting that this is a plant molecule. Just need that isomer fairy, I guess.

Yeah I'm gonna hafta agree here, it basically appears as though at best it may have dissociative properties, as it is as Ham says, the "wrong" enantiomer. It probably is dissociative but I can't fathom how it could have any MOR agonist properties. If I could just open up that portal to the fourth spatial dimension I'd be throwing DXM bottles up and out all day (ya know, half would come back "upside down" as in levomethorphan).

[OxyContinuously]

yeah im w/ you both, hammilton and RJ