Anti-diarrhoea drug drives cancer cells to cell death
aktuelles.uni-frankfurt.de
Anti-diarrhoea drug drives cancer cells to cell death
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Re: Anti-diarrhoea drug drives cancer cells to cell death
#2You mean... it induces apooptosis?
Re: Anti-diarrhoea drug drives cancer cells to cell death
#3A point of interest, not mentioned in the article, is that loperamide is actually an opioid. All opioids cause some degree of constipation, hence why loperamide helps with diarrhea. Loperamide is unusual, in that it doesn't cross the blood-brain barrier, hence why taking it doesn't get you high.
Re: Anti-diarrhoea drug drives cancer cells to cell death
#4How does it not also drive regular cells to death?
Re: Anti-diarrhoea drug drives cancer cells to cell death
#5Sooo, opiates have an anti-diarrhea action by slowing down the intestines/Bowel movements, which is why they cause constipation.
Loperamide is an opiate that acts locally (and probably via the bloodstream too) on the intestines, but doesn’t get into the brain, so you get the anti-diarrhea effects without pain relief/getting high/slow breathing of opiates.
Some randos on the internet believe that you could consume a bottle of loperamide and overcome that inability to get into the brain. In theory that’s true (since the brain barrier is actively pumping it back out and there’s gotta be a limit to that rejection), but I don’t think it’s worked out in practice other than causing massive constipation.
The article touches on this:
> In future studies it has to be explored, for example, how loperamide can be transported into the brain and cross the blood-brain barrier. > Nanoparticles might be a feasible option.
But it remains to be seen what opiate-like effects it would have on the brain if it got through.
For a short-term treatment, this could be managed/mitigated. Mechanically (this machine will breathe for you while we knock out your drive to breathe) or chemically: an opiate-antagonist (naloxone infusion or naltrexone tablets). Whether this would counteract the effect of loperamide remains to be seen.
I also wonder what made loperamide special or if opiates in general would have the same effect. It would be interesting to see if long-term opiate users get this particular tumour less.
Re: Anti-diarrhoea drug drives cancer cells to cell death
#6Several classes of opioids have been shown to cause neuronal degeneration via ATF4 activation. So, key points:
1. Loperamide is not unique. I don't know why these researchers have singled it out. Is it because they heard there's an opioid that doesn't get you high? It only avoids getting you high because it doesn't get into the brain. IF you deliver it to the brain to treat a brain tumor, it will get you high.
2. Patients with GBM already get a shit-ton of opioids for pain, which do cross the blood-brain barrier. Is there any reason at all to imagine that this opioid, using the same mechanism as other opioids, if delivered the area other opioids already reach, will have a different outcome?
3. I don't understand why identifying that loperamide causes cell death via ATF4 is even worth publishing. "Opioid that causes cell death uses same mechanism as other opioids that induce cell death"? Maybe I'm missing something here?
4. This was published in Autophagy. Which is another way of saying it wasn't novel enough to be published anywhere anyone reads. Which is why this is a university press release, and not a discussion by anyone else.
Re: Anti-diarrhoea drug drives cancer cells to cell death
#7Sooo, opiates have an anti-diarrhea action by slowing down the intestines/Bowel movements, which is why they cause constipation. Loperamide is an opiate that acts locally (and probably via the bloodstream too) on the intestines, but doesn’t get into the brain, so you get the anti-diarrhea effects without pain relief/getting high/slow breathing of opiates. Some randos on the internet believe that you could consume a b…
> Some randos on the internet believe that you could consume a bottle of loperamide and overcome that inability to get into the brain. In theory that’s true (since the brain barrier is actively pumping it back out and there’s gotta be a limit to that rejection), but I don’t think it’s worked out in practice other than causing massive constipation.
It's a medication that gets stolen by drug users which is a bit frustrating if it's not working for them.
BNF and Department of Health (England) don't describe addiction to loperamide, but do describe its use as an adjunctive treatment for people trying to come off opioids, which suggests it's not that problematic: https://bnf.nice.org.uk/treatment-summary/substance-dependen...
https://assets.publishing.service.gov.uk/government/uploads/...
> Prescribing symptomatically can reduce some of the physical effects of withdrawal. There is no systematic evidence that any of these medicines work to improve outcome but they may be useful for the clinician in situations where it is not possible to prescribe effective opioid substitution. Particular care is needed concerning the risks of polypharmacy and ensuring appropriate supervision and support in such cases.
> •Diarrhoea – loperamide 4mg immediately followed by 2mg after each loose stool for up to five days; usual dose 6-8mg daily, maximum 16mg daily.
Re: Anti-diarrhoea drug drives cancer cells to cell death
#8How does it not also drive regular cells to death?
"Normally, autophagy regulates normal metabolic processes and breaks down and recycles the valuable parts of damaged...cell components thus ensuring the cell’s survival...In certain tumour cells, however, hyperactivation of autophagy destroys so much cell material that they are no longer capable of surviving."
Re: Anti-diarrhoea drug drives cancer cells to cell death
#9How does it not also drive regular cells to death?
I don't know if chronic opioid exposure drives other cells to death. It certainly does cause some neuronal death, which we've already established with other opioids, also using the ATF4 mechanism. The tumor in this paper is a brain tumor.
AKA, drug belonging to [drug class] that kills [neuronal tissue] will also kill [bad neuronal tissue] through same mechanism as [general drug class].
The key question is "if putting a shit-ton of opioids (which already cross into the brain) in cancer patients doesn't already meaningfully treat this condition, why do we imagine that delivering the same class of drug past the blood-brain barrier suddenly will?"
Having worked in a breast cancer lab once upon a time, I can tell you: because run-of-the-mill cell biology doesn't get grant funding if you don't attach "early cancer diagnostics" or "potential cancer treatment" to the grant application.
Re: Anti-diarrhoea drug drives cancer cells to cell death
#10You mean... it induces apooptosis?
Ouch :)