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B-Carboline alkaloids bind to dna

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Some molecules intercalate with your DNA, proflavine is one of them. Compare its structure to harmine, and it doesn't seem so outlandish that harmalas do the same. I recently went back through that section in the invisible landscape, it is very dense but I think I understand what he was getting at- I think he was trying to construct another model of drug interaction to help explain the subjective changes experienced while tripping. The general idea, and I could be way off base, is that the intercalation of molecules with ones DNA would result in an altered electron spin resonance, which i interpreted as a general vibratory change from your baseline - you're awareness or perception of this vibratory change could account for some of the effects experienced on psychedelics. I have found articles suggesting LSD intercalates with DNA, and have also found articles suggesting that it doesn't - so I'm not sure how far we can entertain the idea.

The question I have is, what effect does the intercalation of molecules with the DNA have on the replication of DNA? Is the replicated DNA modified or mutated in some way as a result of the temporary bond with the intercalated molecule?
 
 
narmz said:
Some molecules intercalate with your DNA, proflavine is one of them. Compare its structure to harmine, and it doesn't seem so outlandish that harmalas do the same. I recently went back through that section in the invisible landscape, it is very dense but I think I understand what he was getting at- I think he was trying to construct another model of drug interaction to help explain the subjective changes experienced while tripping. The general idea, and I could be way off base, is that the intercalation of molecules with ones DNA would result in an altered electron spin resonance, which i interpreted as a general vibratory change from your baseline - you're awareness or perception of this vibratory change could account for some of the effects experienced on psychedelics. I have found articles suggesting LSD intercalates with DNA, and have also found articles suggesting that it doesn't - so I'm not sure how far we can entertain the idea.

The question I have is, what effect does the intercalation of molecules with the DNA have on the replication of DNA? Is the replicated DNA modified or mutated in some way as a result of the temporary bond with the intercalated molecule?
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Awesome dude, honest thanks for sharing! Peace...
 
Ljosalfar said:
I must second the call for empiricism! It is fun and stimulating to conflate our drug experiences with what the chemicals may be doing bio-chemically, but conclusions reached in this fashion are often outside the realm of testable hypothesis. We simply don't know enough - a rather heartening state of affairs, if you ask me!
Harmalas are not so novel - many poisons, alkaloids included, interact with DNA.
L
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I agree, I wasn't jumping to conclusions and i always think we should avoid this..I was just noting some curious related things and throwing some wild thoughts out there


"Harmalas are not so novel - many poisons, alkaloids included, interact with DNA."

I don't agree with this at all though. I mean that's like saying eating psilocybin mushrooms isn't so novel because other mushrooms are poisonous. Some mushrooms have amazing medicinal qualities just like some molecules that bind to DNA have beneficial functions, while some don't. I think harmalas are extremely novel..drink 120grams of banisteriopsis caapi tea and lay down in silent darkness if you don't think so and haven't yet. They are very therapeutic and unique psychedelics on their own and basically nothing I've seen indicates that harmalas are dangerous, while A LOT of traditional practices, anecdotal reports, and research indicates exactly the opposite..look at what i quoted in post #8

and i mean thats not even going into the double helix motif/archetype seen within shamanic traditions worldwide, and probably most intensely in ayahuasca experiences/communities..or the fact that syrian rue seems to be a prime candidate for soma (or is it soma? do we know for sure? I've heard conflicting things and can't remember) I'm also not aware of any other psychedelics that bind to DNA, so if anyone has any information on that please by all means post it up :)
 
okay so what about this from wikipedia..

"Use of topoisomerase inhibitors for antineoplastic treatments may lead to secondary neoplasms because of DNA damaging properties of the compounds. Also plant derived polyphenols shows signs of carcinogenity, especially in fetuses and neonates who do not detoxify the compounds sufficiently.[11][12][13] An association between high intake of tea (containing polyphenols) during pregnancy and elevated risk of childhood malignant central nervous system (CNS) tumours has been found."

Can we really generalize in that way? Can we assume that because harmine is a topoisomerase inhibator that long term frequent use can be carcinogenic?

Would this be dose dependant?

What is concidered a dose toxic enough that the body would need some time to "detox"?

Not that I think harmine is carcinogenic, becasue I think it probly is not..just wondering how easy it really to generalize something like..
 
Topoisomerase inhibitors is almost always bad news for dividing cells. Thankfully the majority of your cells in our bodies are non-dividing, as opposed to cancer cells that are dividing like crazy. I'd agree with jamie that with harmine there must be an optimum dosage where harmine harms the cancer cells more than the body - this is the strategy of most chemotherapies and radiotherapies in cancer treatment.

Still some caution should be exercised since topoisomerase inhibitors are potentially mutagenic. To what extent this applies to harmine, we do not know further than these theory bits; I wouldn't extrapolate and generalise on the potential carcinogenicity but I wouldn't go overboard flooding myself with 200-300mg harmine daily either.
 
so I found this link that seems to suggest that at least extracts of rue can actaully aid in mitosis..

www.ncbi.nlm.nih.gov

Effect of Peganum harmala extract on root tips of Allium cepa - PubMed

Treatment with Peganum harmala extract remarkably increased the mitotic index in Allium cepa root tips with increasing treatment duration at all exposure times used and with almost all concentrations. The extract caused a relatively high increase in the mitotic index after a long period of...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

So what is going on here? If topoisomerase is being inhibited shouldn't that inhibit mitosis and not aid in mitosis??
 
Topoisomerase enzymes take part in the progression of mitosis, or in other words cell replication by aiding DNA replication. If you inhibit topoisomerases then you're going to stall DNA replication and induce a DNA damage checkpoint, that is the cell cycle will be "fixed" into the DNA replication stage till the problem is solved. By doing so, by definition you increase the mitotic index, i.e.with harmalas you're going to have cells not exactly dividing but stuck in the division stage and more cells will appear as "replicating". But in reality they're stuck in a dead-end and won't finish replication.

It's like saying that face-lifting makes you happy because it can inadvertently make you appear as "smiling"
 
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