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Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

societyforscience.org

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Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#151

Post by throwawaymaths »

gus_massa wrote: post #150
throwawaymaths wrote: post #4

impressive for a high schooler but this just adds a protecting group onto tylenol. am i missing something? edit: oh i see. its really blurry but the silyl modified tylenol is predicted to have good trpv1 binding computationally. afaict no in vitro or in vivo studies were done. could be cool. not sure if diethylethynylphenylsilyl group has good Lipinski properties though (i suspect not) edit: s/aspirin/Tylenol

[Very good comment! I'd use the opportunity to add more questions.] How expensive are the steps? They look like advanced steps that can be done in a lab to prepare a few micrograms, but I'm not sure if they can be scaled to industrial production. Why silicon instead of just a carbon? Is it better blocking the docking? Is it better moving the orbital energy levels? Is it as safe as the poster claim?

silicon is not very successful in drugs.

https://www.science.org/content/blog-post/silicon-drug-molec...

that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy)

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#152

Post by cluckindan »

Ey7NFZ3P0nzAe wrote: post #144
cluckindan wrote: post #76

Earlier quoted context omitted.

Prescribing cannabis for pain also leads to less morphine consumption.

The safety profile of paracetamol is orders of magnitudes higher ghan cannabis though. It is still one of the, if not the, most heavily used and appreciated drug and can be taken at any age

That is untrue. Did you read the OP article? Just 10 standard 500mg tablets of paracetamol in 24h will cause irreversible liver damage.

It’s the exact opposite of what you claim. Cannabis is orders of magnitude less destructive to the body than paracetamol.

If you honestly believe what you wrote, you need to check your sources. There is a lot of drug war propaganda still out there.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#153

Post by const_cast »

adamredwoods wrote: post #139
Mizza wrote: post #3

She didn't even break the top 10 in this content: https://www.societyforscience.org/regeneron-sts/2025-student... I'm impressed beyond words by these kids, though I think I'd give her the top prize. Watching my grandfather's final days taken away from him by the effects of morphine has always made me wish so much that we had much more effective non-narcotic painkillers

I'm pro-morphine as a controlled medicine for extreme pain and end-of-life. I've seen it work. I've had it post-surgery. Fentanyl, my brother claims to be the best. It, too, can work wonders under a controlled environment.

Fentanyl is pretty much better than morphine in every way. Less toxic, cheaper, and works better with less side-effects. Especially less histamine response, which is the body itching people get.

Unfortunately, it's tainted by illicit use. Damned to only be used in dire circumstances. It's a shame, really.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#154

Post by const_cast »

AStonesThrow wrote: post #28
fracus wrote: post #18

Earlier quoted context omitted.

I thought morphine didn't cause health damage to the human body apart from addiction and withdrawal symptoms.

Nurses in palliative care and hospice are well-known to generously administer morphine in increasing doses, because it eventually takes away all the pain and suffering (of the families and nurses).

.. and of the patient. Being in pain, especially constant pain, sucks major ass. People who haven't gone through that don't really know. You can't just ignore it so, in turn, it occupies every space in your brain. We don't realize how many functions we possess that require the precondition of some level of comfort.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#155

Post by Ey7NFZ3P0nzAe »

cluckindan wrote: post #152
Ey7NFZ3P0nzAe wrote: post #144

Earlier quoted context omitted.

The safety profile of paracetamol is orders of magnitudes higher ghan cannabis though. It is still one of the, if not the, most heavily used and appreciated drug and can be taken at any age

That is untrue. Did you read the OP article? Just 10 standard 500mg tablets of paracetamol in 24h will cause irreversible liver damage. It’s the exact opposite of what you claim. Cannabis is orders of magnitude less destructive to the body than paracetamol. If you honestly believe what you wrote, you need to check your sources. There is a lot of drug war propaganda still out there.

indeed I have not been specific enough: I meant "at therapeutic dosage". Thank you for keeping me in check!

Acetaminophen indeed has a shitty therapeutic index and cannabis in any (natural) form has basically no acute toxicity.

But i'd take 1g of acetaminophen daily for the rest of my life starting at age 1 instead of taking 1 cannabis joint equivalent every day. And that's even if we're talking edible form or vaping (i.e. not considering tars).

What about you?

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#156

Post by abridges6532 »

const_cast wrote: post #154
AStonesThrow wrote: post #28

Earlier quoted context omitted.

Nurses in palliative care and hospice are well-known to generously administer morphine in increasing doses, because it eventually takes away all the pain and suffering (of the families and nurses).

.. and of the patient. Being in pain, especially constant pain, sucks major ass. People who haven't gone through that don't really know. You can't just ignore it so, in turn, it occupies every space in your brain. We don't realize how many functions we possess that require the precondition of some level of comfort.

As someone young with chronic pain issue but otherwise healthy , obviously increasing doses of opioids or really any opioids at all. This aspect of it occupying every space of your brain can be true in this case as well. It’s hard to compartmentalize and still go about your daily life while no one can see the anguish your in.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#157

Post by gus_massa »

throwawaymaths wrote: post #151
gus_massa wrote: post #150

Earlier quoted context omitted.

[Very good comment! I'd use the opportunity to add more questions.] How expensive are the steps? They look like advanced steps that can be done in a lab to prepare a few micrograms, but I'm not sure if they can be scaled to industrial production. Why silicon instead of just a carbon? Is it better blocking the docking? Is it better moving the orbital energy levels? Is it as safe as the poster claim?

silicon is not very successful in drugs. https://www.science.org/content/blog-post/silicon-drug-molec... that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy)

[Sorry for the delay.]

IIUC from the "In the pipeline" article, drugs with silicon are too similar to their equivalent with carbon, and more difficult to make: "so why bother?"

Are they using the silicon to avoid the usual rules of substitutions in benzene cycles? Is it possible to do the same trick with carbon?

> that molecule almost certainly fails the ClogP not greater than five lipinski rule (it's too greasy)

Is it possible to fix it adding some -NH2 (or -COOH ?) group in the second aromatic cycle?

[I understand it's a nice science fair project but the article oversell it.]

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#158

Post by atombender »

cma wrote: post #143
shawabawa3 wrote: post #136

Earlier quoted context omitted.

I'm pretty sure ibuprofens risks are significantly higher than a 10-20% increased risk of dementia, it gives significantly increased risk of strokes iirc

I thought NSAIDs thinned blood more like apsirin and gave aneurysm risk instead of stroke, and the big risk was stomach bleeds.

NSAIDs are COX inhibitors which inhibit either COX-1, COX-2, or both.

COX-1 is involved in the gastric mucosa, among other roles, which is why blocking it can cause stomach bleeding.

COX-2 is involved in maintaining the endothelium of blood vessels, and can increase stroke and infarction risk by stiffening and degrading the lining of the blood vessels over time.

Studies are a bit conflicting regarding whether blocking COX-1 or COX-2 is safer, as there seems to be downsides to both, and the difference in risk isn't that clear.

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#159

Post by Rastonbury »

AnthonBerg wrote: post #141
Rastonbury wrote: post #125

Earlier quoted context omitted.

I take NAC to help with hangovers, I used to get smashing headaches and people would recommend random Korean and japanese 'hangover supplements', I was obviously very skeptical and googled every ingredient to check it is safe. The ones that worked had NAC or gluthanione. Looked into it and bought some and always take it when I drink or have panadol. Have not noticed any other subjective effects Nausea or vomitting is…

Interesting!, thanks! NAC is all over the place; I didn’t know about this application. And yeah I was 100% skeptical too! Now I’m more sceptical of the kinda “nothing is known, nothing is knowable” angle, you know? There is so much knowledge, actionable, often unread, often unused. (Have to mention it, if useful: Na—R-ALA (alpha lipoic acid) and ambroxol are kind of in the same vein. Ambroxol is strangely a sort of b…

That's interesting I took r-ALA before, cannot recall dosage but felt nothing of that sort or subjective/psychoactive at all. Several people I know report acute changes too when taking lion's mane but I don't

Re: Modification of acetaminophen to reduce liver toxicity and enhance drug efficacy

#160

Post by AnthonBerg »

Rastonbury wrote: post #159
AnthonBerg wrote: post #141

Earlier quoted context omitted.

Interesting!, thanks! NAC is all over the place; I didn’t know about this application. And yeah I was 100% skeptical too! Now I’m more sceptical of the kinda “nothing is known, nothing is knowable” angle, you know? There is so much knowledge, actionable, often unread, often unused. (Have to mention it, if useful: Na—R-ALA (alpha lipoic acid) and ambroxol are kind of in the same vein. Ambroxol is strangely a sort of b…

That's interesting I took r-ALA before, cannot recall dosage but felt nothing of that sort or subjective/psychoactive at all. Several people I know report acute changes too when taking lion's mane but I don't

Interesting, right?

As a detail, I clearly experience the better bioavailability of Na-R-ALA. Often marketed as “stabilized”. As well as what I believe is the increased bioavailability of Na-R-ALA dissolved in water.

The main point I wanted to make is that it occurred to me when reading your comment that I know myself to be somewhat “oxidatively burdened”, if that’s a term? I have mild psoriasis, which is known to use oxidative and redox capacity in the immune system’s activation in the rash. (afaik immune cells “fire bullets” of oxidization at perceived intruders.) There are other stressors in my life which are also inherently oxidising in the molecular biology of it. I’d bet a nice bottle of Oban that that is a factor in the sense of relief.

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