Need help, anyone knows safe cytochrome P450 inhibitors? Needed for demethylation treatment

Therapeutic Efforts
#1

Hello everyone.

As u may know I want to trial a demethylation substance called RG108. According to the link mentioned below, ketoconazole is used for its P450 inhibiting properties. Ofcourse I won’t use that because of its anti-androgen and AR inhibiting properties. Still, I need a P450 inhibitor for sufficient effect of the RG108. I was wondering if any of you know something, or have any knowledge they can add. Also, the article is a very interesting read. So if you are interested in demethylation, u could try and read it.

Tagging the guys with knowledge again haha: @awor @axolotl @Dubya_B
https://onlinelibrary.wiley.com/doi/full/10.1111/bcpt.12514

#2

I am unfortunately very busy so I am not in a position to look into these plans in any detail but I would strongly advise against a P450 inhibitor. p450 is the cholesterol side-chain cleavage enzyme and functions as the first step in steroidogenesis, through which pregnenolone and ultimately, after a number of steps, testosterone is synthesised. This would therefore have an endocrine disruptive effect so is not without risk.

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#3

Ugh, everytime i think i get somewhere, something gets in the way. I will have to think hard about it, since it does seem like it’s the only way to really make the RG108 work, and it’s really my last option. How severe would this effect be? I mean, is it a possibility, or does it have a good chance to cause disruption.

#4

It’s the last option on your shopping list right now - it’s not your last option. We are doing our best for a reason, after all :slight_smile:

I cannot tell you how severe it would be. From my personal observations it appears that a lot of the time severe cases who got “PFS” from very little are at most risk of rapid further worsening with further endocrine disruption. Some cases seem quite resilient to further permanent worsening and take things that would finish me off. The problem with these risks is there is no time machine if there’s a persistently negative outcome, and as much as it’s easy to say “well what else can I do”, the outcome of self-therapies has sometimes been patients left in a condition where they have committed suicide, so I’m sure you’ll understand why the staff of this forum suggest a highly cautious approach in regards to what we know and dont know about fiddling with this critical pathway. As no safe and effective therapy is known, the rationale for self-therapies and decisions regarding that can only be up to the individual.

best

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#5

Thanks, and yeah, I already fucked myself up with such things (betaine )making it undoable to just wait longer, I am done. That’s why I say, fuck it, I do this because i really believe in it, and life has become intolerable already. I am very prone to further disregulation so it scares me nonetheless. I have this btw: ‘‘Additionally, it has been associated with cytochromes in high‐throughput screening experiments (CYP2C19 substrate, CHEMBL1613777) and induced CYP1A2 and CYP1B1 in own unpublished data. Here, we sought to establish the pharmacokinetics of RG 108 in a rat model in the absence and presence of cytochrome P450 inhibition.’’

Maybe there is a way around? thanks for the reply btw

#6

Off hand, and maybe I’m wrong about this, but grapefruit juice?

Like @axolotl said, it can always get worse. You and me both learned this the hard way.

By the way! How in the hell do these methyl donors do us so much harm on their own? This leans me toward believing induction of demethylases or demethylase inhibitors can help.

How many have tried this though?

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#7

Yeah was also thinking about that one. It inhibits a specific one though. But taking a p450 inhibitor really seems like a no go, i think it has good potential of worsening me significantly.

#8

Anonymous1968 has tried methylprednisone and it seems to have helped him. However, he did have some sleeping problems. But he is one of the rare people on this forum who has recovered quite a bit.