So let’s talk about isoquinolines

[Rabbit]

@Xorkoth Do you still have friends at Erowid? I can run this book through an OCR application and get it into text/html. Would they be interested in putting it on erowid if I do that for them?

 

[G_Chem]

It seems like this one is so expensive because they only did one run of hardbacks and it was never re-printed. Maybe we should reach out to Ann and see if it would be possible to get a second edition printed in paperback? How many of you would be willing to chip in for this? I'd love to have a copy in hardback. I plan on writing her soon I'll ask about it. With all the crowd funding websites out there now it wouldn't be hard to come up with enough people to chip in assuming she has the rights to the book.

If I find a copy that doesn't cost an arm and a leg I'll have it re-scanned for a cleaner PDF. If Ann has the rights I know of a few print shops still in business that would produce a small run of 1,000 or so for me. It doesn't cost as much as you might think.

I haven't gotten a chance to thumb through this yet because I hate reading books on a computer but from what I saw the pdf I posted is readable. Don't assume the link will work for long I think that website regularly clears files to make room for new ones. If the link dies I'll re-upload it.

Much appreciated man, unfortunately I can’t pitch in but I’ll buy one when/if they’re ready

Great ideas though, I don’t see why she would say no... I’d be willing to write her too if it helps.

I agree I absolutely despise reading books online, hence my desire to find one.


As for some of these compounds, are any located in any easy to access plants where we could get to it with potential bioassays?

-GC

 

[Rabbit]

Not trying to derail this too much but on the subject of books/pdfs: If you own a decent printer you can print off this pdf file and put the pages in a cheap binder. I've done this for a lot of rare books. When I used to have more equipment set-up I'd do small runs of rare books with nice paperback covers. I no longer own a binding machine and other stuff because a hustling preacher swindled us out of a lot of money. I still have thousands of the books he ordered just laying around and they're useless to anyone that wasn't connected to his (for lack of a better word) cult. I'll never forget that smug asshole swaggering in and sweet talking my grandmother out of thousands of dollars. He was a big reason why I turned my back on religion for so many years. He's one of the main reasons why the place would go out of business in the late 90s.

I'm going to reach out to Ann sometime at the start of the next month. In the mean time I'll try to OCR this book and get it into a more readable format. I'll try to contact the guys at Erowid when I can because this needs to be up with his other books on their website.

 

[Rectify]

I sold my copy some years ago for very much less money.

 

[ions]

There’s also the shulgin index which goes for several hundred dollars. I would and have pitched in to shulgins writings and lab.

 

[Neuroborean]

As for some of these compounds, are any located in any easy to access plants where we could get to it with potential bioassays?

For the sake of psychonaut science I must resurrect this thread for a while...

I was trying to find some other atypical opioids in natural sources so I found Chelidonium and Corydalis as sources of different interesting isoquinolines, somewhat similar to aporphine type alkaloids, corydine and corydaline
In fact there's quite a bunch of different plants with those alkaloids in different forms (analog-like). it would be very nice to try to extract one of those:

Identification and characterization of plant-derived alkaloids, corydine and corydaline, as novel mu opioid receptor agonists - Scientific Reports

Pain remains a key therapeutic area with intensive efforts directed toward finding effective and safer analgesics in light of the ongoing opioid crisis. Amongst the neurotransmitter systems involved in pain perception and modulation, the mu-opioid receptor (MOR), a G protein-coupled receptor...

www.nature.com

"we report on the discovery of two naturally occurring plant alkaloids, corydine and corydaline, as new MOR agonists that produce antinociceptive effects in mice after subcutaneous administration via a MOR-dependent mechanism. Furthermore, corydine and corydaline were identified as G protein-biased agonists to the MOR without inducing β-arrestin2 recruitment upon receptor activation. "

much likely they are not as strong as kratom alkaloids, but that doesn't mean we couldn't try to extract them to a point of making them somewhat interesting, at least in non-recreational (pharmacological) ways. Or well, if I would be able I would study chemistry and pharmacy to try to make some analogs, but well, my time it's limited!

from the paper:
"Mapping of these features was therefore chosen as requirement for virtual hits in order to be subjected to experimental testing. Based on the current results, we have selected seven natural products, corydine (1), corydaline (2), bulbocapnine (3), thalictricavine (4), bernumidine (6), intebrimine (7) and capnosinine (8), and one natural product analogue, 2-(2,3-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (9) (Figs. 2 and 3) for further investigations."

Didn't check if all those are isoquinolines, to be honest, but it's interesting enough to list them, I guess.
Bad news is that in mouse models corydine is 10 times less effective than morphine in antinociception models...

Some natural sources are Chelidonium, Berberis and Corydalis

Some interesting plants:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704877/ CORYDALIS YANHUSUO, with tetrahydropalmatine, glaucine and corydaline

https://pubmed.ncbi.nlm.nih.gov/29713277/
https://www.florajournal.com/vol3issue1/may2015/2-6-10.1.pdf CHELIDONIUM MAJUS, packed with different alkaloids and compounds including corydine and nor-corydine (this could be toxic so I need more investigation on them, as with the berberis genus

 

[G_Chem]

For the sake of psychonaut science I must resurrect this thread for a while...

I was trying to find some other atypical opioids in natural sources so I found Chelidonium and Corydalis as sources of different interesting isoquinolines, somewhat similar to aporphine type alkaloids, corydine and corydaline
In fact there's quite a bunch of different plants with those alkaloids in different forms (analog-like). it would be very nice to try to extract one of those:

Identification and characterization of plant-derived alkaloids, corydine and corydaline, as novel mu opioid receptor agonists - Scientific Reports

Pain remains a key therapeutic area with intensive efforts directed toward finding effective and safer analgesics in light of the ongoing opioid crisis. Amongst the neurotransmitter systems involved in pain perception and modulation, the mu-opioid receptor (MOR), a G protein-coupled receptor...

www.nature.com

"we report on the discovery of two naturally occurring plant alkaloids, corydine and corydaline, as new MOR agonists that produce antinociceptive effects in mice after subcutaneous administration via a MOR-dependent mechanism. Furthermore, corydine and corydaline were identified as G protein-biased agonists to the MOR without inducing β-arrestin2 recruitment upon receptor activation. "

much likely they are not as strong as kratom alkaloids, but that doesn't mean we couldn't try to extract them to a point of making them somewhat interesting, at least in non-recreational (pharmacological) ways. Or well, if I would be able I would study chemistry and pharmacy to try to make some analogs, but well, my time it's limited!

from the paper:
"Mapping of these features was therefore chosen as requirement for virtual hits in order to be subjected to experimental testing. Based on the current results, we have selected seven natural products, corydine (1), corydaline (2), bulbocapnine (3), thalictricavine (4), bernumidine (6), intebrimine (7) and capnosinine (8), and one natural product analogue, 2-(2,3-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (9) (Figs. 2 and 3) for further investigations."

Didn't check if all those are isoquinolines, to be honest, but it's interesting enough to list them, I guess.
Bad news is that in mouse models corydine is 10 times less effective than morphine in antinociception models...

Some natural sources are Chelidonium, Berberis and Corydalis

Some interesting plants:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704877/ CORYDALIS YANHUSUO, with tetrahydropalmatine, glaucine and corydaline

https://pubmed.ncbi.nlm.nih.gov/29713277/
https://www.florajournal.com/vol3issue1/may2015/2-6-10.1.pdf CHELIDONIUM MAJUS, packed with different alkaloids and compounds including corydine and nor-corydine (this could be toxic so I need more investigation on them, as with the berberis genus

Now it all depends on the quantity found in the plant, if it’s worth extracting. I’ve heard Corydalis as psychoactive but never that it was a MOR agonist. The lack of potency is sad but maybe some other similar alkaloids present are stronger, or some (hopefully) easy chemical manipulations to something stronger.

I think that may be the future of illicit drugs, finding natural substances which may not be 100% what we are looking for but then knowing the direction to take them to make something greater. Heroin being a prime example compared to morphine.

-GC

 

[Neuroborean]

I’ve heard Corydalis as psychoactive but never that it was a MOR agonist.

yeah, I guess it's because of the amount of corydine that's there, probably there's some papers in pubmed to find the better sources for all those, or some natural "analog" that's stronger than the basic stuff.
The main active in Corydalis is tetrahydropalmatine, I was watching a thread about it right now.

 

[Allylbenzene]

Identification of Sassafras albidum alkaloids by HPTLC/DESI-MS and mapping by DESI-MSI

Sassafras albidum is an important tree species that occurs across North America. The presence of benzylisoquinoline and aporphine alkaloids has been previously described
...
A total of 12 alkaloids were indentified in the roots and twigs, and six of them were detected for the first time in S. albidum. ...five aporphines and seven benzylisoquinolines.
...
All alkaloids seem to accumulate more in the outer layers of Sassafrass albidum roots
...
Coclaurine, N-methyl coclaurine, and armepavine...are described here for the first time in the genus sassafras.
...found in the roots: norcinnamolaurine, cinnamolaurine, boldine, reticuline.
...
The two alkaloids with a methylenedioxy group identified in this work: norcinnamolaurine and cinnamolaurine

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/jms.4674

Cinnamolaurine

My only experiences with "sassafras" has been alkaloids extracted from the sassafras root. Some time ago, the chemists doing the MDMA syntheses realized they could do an A/B/NP extraction from the leftover juice in their steam stills to produce an alkaloid extract with similar but much less intense effects as MDMA.

I have written about this material several times and generally been met with disbelief. Everyone thinks that the drug myths they've always believed ever since they were kids is true, and the idea that Sass=MDA is one of them. I have personally extracted and consumed this material, and I have received the identical material from others who have extracted it, and yes they called it Sassafras, because that's the plant it's extracted from.

The chemical proposed to be responsible for the effects of sassafras alkaloid extracts is cinnamolaurine. You can look it up, there's a wealth of info about it, although there is not a wealth on its pharmacology. I performed an experiment where I extracted alkaloids from two different species of cinnamon (which according to much literature, contains cinnamolaurine). The effects of these extracts were very similar to sassafras alkaloids. The differences can be explained by the different alkaloid profiles in each plant.

https://forum.dmt-nexus.me/threads/sass-organic-ecstacy-is-complete-bullshit.319428/post-3472470