Treating Brain Cancer with a $50 Antidepressant? Drug Repurposing in Glioblastoma

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  • Опубликовано: 24 дек 2024

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  • @totalsynthesis
    @totalsynthesis  2 месяца назад +11

    Hey there - thanks for watching! Let me know how you liked the video and if you have any questions or suggestions.
    Thanks to all my channel supporters! www.patreon.com/totalsynthesis | instagram.com/totalsynthesis_official/

    • @stefanschleps8758
      @stefanschleps8758 2 месяца назад

      Brain tumors? Does Selegiline demonstrate antitumor action? Is it neuroprotective?

  • @fatman9644
    @fatman9644 2 месяца назад +8

    I think it can be really helpful for certain patients, I mean SSRIs are only helpful to some depressed patients, but if a patient has cancer, gets depressed because of that, then an antidepressant which not only improves your mood but also lenghtens your survival would be insane, however only time will tell, whether this will be the case for how many patients

    • @totalsynthesis
      @totalsynthesis  2 месяца назад +1

      Yes spot on. Nice profile pic 😂

  • @squareacid
    @squareacid 2 месяца назад +55

    So Temozolomide is gone be the next Explosion & Fire vid? i guess

    • @bushhawk5460
      @bushhawk5460 2 месяца назад +8

      Call it "Fighting cancer with explosives" or something like that.

    • @some_haqr
      @some_haqr 2 месяца назад

      Ah man i fucking hope so now dude

  • @Fiberoptic11
    @Fiberoptic11 Месяц назад +3

    Any possible new cure is great to hear. I currently have grade 4 glioblastoma. I’ve been through all the radiation treatments I can have, 2 surgeries and it’s still growing while taking Temozolomide. I’m getting switched to gleostine soon. Been fighting this evil since 2019.

    • @totalsynthesis
      @totalsynthesis  Месяц назад +1

      Oh man. Keep fighting! I wish you the best of luck and strength

    • @opinair
      @opinair 5 дней назад

      Try to fast day by day, and when you eat, don't eat too much-only the minimum necessary. The best option is to focus on foods containing chlorophyll and vegetables. Avoid sugars and unnatural foods. Make a serious effort to eat as little as possible. In this way, you will force your body to consume the cancer, rather than letting the cancer consume your body.

  • @-r-495
    @-r-495 2 месяца назад +8

    Prozac was described as a drug with anti-inflammatory effects by Edward Bullmore in his book Inflamed Mind.
    Personally, I am not a fan of anti-depressants but am happy if they work for others.
    Very interesting video as always, thank you!

    • @totalsynthesis
      @totalsynthesis  2 месяца назад +1

      Thanks!

    • @Lock484
      @Lock484 2 месяца назад

      They've worked for me... For a few months 😐. Then I've got almost back to baseline, and the psychiatrists solution for that was to double my dose... For a few months again, until it stopped again, and they wanted to up my dosage again 😩. I've decided against that, and just stopped taking it... For about 48-60 hrs, after which I've had to take the pill again, because the wd was absolutely disgusting 😢. This has started me on a prolonged tapering, in which I've shaved off a portion of the pill every 3 days to eventually stop taking it at all... And I've still felt absolutely horrible when I stopped having it in my system 😭.
      Honestly, it was one of the worst wd experiences I've had, and I've had a moderate oh-pee-oid and severe kratom habit. So yeah, definitely not a fan of antidepressants either, it's mechanism of action IS addiction/dependence in my opinion, they're just betting on your high self will feel better than the sober self, and that is definitely not always guaranteed, or can change a lot over time 😓.

    • @Lock484
      @Lock484 2 месяца назад

      They've worked for me... For a few months 😐. Then I've got almost back to baseline, and the psychiatrists solution for that was to double my dose... For a few months again, until it stopped again, and they wanted to up my dosage again 😩. I've decided against that, and just stopped taking it... For about 48-60 hrs, after which I've had to take the pill again, because the wd was absolutely disgusting 😢. This has started me on a prolonged tapering, in which I've shaved off a portion of the pill every 3 days to eventually stop taking it at all... And I've still felt absolutely horrible when I stopped having it in my system 😭.
      Honestly, it was one of the worst wd experiences I've had, and I've had a moderate oh-pee-oid and severe kratom habit. So yeah, definitely not a fan of antidepressants either, it's mechanism of action IS addiction/dependence in my opinion, they're just betting on your high self will feel better than the sober self, and that is definitely not always guaranteed, or can change a lot over time 😓.

  • @chemistryofquestionablequa6252
    @chemistryofquestionablequa6252 2 месяца назад +18

    This is possibly the ONLY reason I'd take Prozac after reading the trials that got it approved. I occasionally infuriate doctors by refusing "off label" prescribing. I'd much rather have a medication for it's intended purpose than for it's interesting side effects.
    Mostly excited to discover a new energetic here!

    • @pocpic
      @pocpic 2 месяца назад +3

      you're missing out.

    • @chemistryofquestionablequa6252
      @chemistryofquestionablequa6252 2 месяца назад +3

      @@pocpic nah, I've tried a lot of the common "off label" Rx meds and antidepressants.

    • @timecode37
      @timecode37 2 месяца назад

      @@chemistryofquestionablequa6252 why do you refuse them? do the off-label medications just not work as well or do they work but the side effects aren't tolerable?

    • @-bamks
      @-bamks 2 месяца назад

      Off label is made up tbh. It does the same stuff for everyone.

    • @danaveye3977
      @danaveye3977 2 месяца назад

      @@chemistryofquestionablequa6252 SSRIs are neurotoxic. End of story

  • @chemistrycapital
    @chemistrycapital 2 месяца назад +9

    I saw this paper and thought it was super interesting. I think we will see lots more examples of this, especially with the machine learning and "AI" methods being developed.

  • @jhonbus
    @jhonbus 2 месяца назад +11

    0:40 "We've only recently realised it's explosive"
    Jesus, really!? That much nitrogen in one place automatically puts this in the "probably explody" category for me!

  • @OsmioIridio-og8cn
    @OsmioIridio-og8cn 2 месяца назад +5

    Excellent content

  • @martinperales3531
    @martinperales3531 2 месяца назад +4

    Love the coverage of the biology aspects, great

  • @Geneu97
    @Geneu97 2 месяца назад +1

    You got me subscribed on mgmt, dude, why but also yes so cool! Coming from med background very fun video!

  • @MandrakeFernflower
    @MandrakeFernflower 2 месяца назад +8

    Chlorpromazin and trifluoperazin has shown promise in various brain infections
    Might be worth makng a video on?

    • @stevengill1736
      @stevengill1736 2 месяца назад

      They found a new use for thalidomide too....as far as explosive properties of temozolomide, could be...put a pinch on a steel plate & hit it with a hammer.., that'll give you a feel for it.
      There's a similar compound called tetrazene that was used in the past - I've worked with it a long time ago....not particularly dangerous if handled with care. Now there's some heavy metal tetrazenes used experimentally by the US Navy that are closer to lead azide than anything, I mean serious primary explosives! But believe it or not a tap or rubbing the compound with a hanner similarly gives you a good feel for it's sensitivity and brisance....have at it! Cheers...

  • @dariusszablowski5474
    @dariusszablowski5474 2 месяца назад +4

    Great video. Super interesting papers and underlying mechanism. Thank you for the great video. ☺

  • @TheBackyardChemist
    @TheBackyardChemist 2 месяца назад +4

    16:10 I wonder what happened to the sertindole results. Most of the drugs on the ass end of this spectrum had relatively weak activity, but sertindole appears to have some sort of subgroup-selective conflicting effect. On a few patient samples and all three cell lines, it is as effective as VORT, but it makes things worse often and badly enough to be the second worst drug on the list, on average. I wonder if this is just noise, or there is some difference in gene expression that decides if sertindole harms or helps the cancer cells.

  • @andreasholmqvist4422
    @andreasholmqvist4422 2 месяца назад +4

    A missed opportunity to highlight the pivotal role of thalidomide in the discovery and development of PROTACs.

    • @totalsynthesis
      @totalsynthesis  2 месяца назад +2

      I go into degraders at the end of my thalidomide video!

  • @geekswithfeet9137
    @geekswithfeet9137 2 месяца назад +3

    I don’t know how chemist doesn’t realise that is an explosive just by looking at it

    • @totalsynthesis
      @totalsynthesis  2 месяца назад +4

      Never feel too safe around that many nitrogens

  • @kenhaze5230
    @kenhaze5230 Месяц назад +1

    Who looks at that structure (temozolomide) and thinks "no reason to suspect THAT'S explosive!"
    I'm a neuro PhD and that's still one of the more explosive looking molecules I've seen lol.

  • @Psychx_
    @Psychx_ 2 месяца назад +6

    Antidepressants increase BDNF signalling and through that excert neuroprotective effects towards glia cells and neurons. Inflammation gets downregulated, the capability to buffer and withstand oxidative stress increases. BDNF is closely related to actual nerve growth factors/hormones, which could prove as a double edged sword, since it could actually promote the growth of an existing tumor, make it more resilient against treatment and improve its capability of immune system evasion.

  • @abs0lute-zer061
    @abs0lute-zer061 2 месяца назад +2

    I actually got this one on time!

  • @johnthomas2970
    @johnthomas2970 2 месяца назад +1

    I didn’t understand most of the chemistry explained here but if I watch enough of these I’ll get it one day right?

  • @acidangel162
    @acidangel162 2 месяца назад

    They use 50 times higher doses of Vortioxetine than they use for treating depression. For depression you take 10 milligrams. In these tests the mice were given 10 mg per kilogram.

  • @gregorymalchuk272
    @gregorymalchuk272 2 месяца назад

    Prozac is one of the more potent inducers of Brain Derived Neurotrophic Factor.

  • @jairo8746
    @jairo8746 2 месяца назад

    What about pairing the antidepressant with MGMT inhibitors?. Cells would be susceptible regardless if they have the enzyme or not. But i am guessing those inhibitors would be toxic for regular cells all over the body.

  • @morgan0
    @morgan0 2 месяца назад

    0:43 considering those nitrogens, i think it shouldn’t be surprising that it explodes lol

  • @isa-manuelaalbrecht2951
    @isa-manuelaalbrecht2951 2 месяца назад

    It seems Methadon ist very effectful in case of brain tumors..😊

  • @williammcghee863
    @williammcghee863 2 месяца назад +1

    My dad died from this disease; one of his doctor said maybe there will be a cure in fifty years.

    • @totalsynthesis
      @totalsynthesis  2 месяца назад

      Oh man... my condolences

    • @milosmilojevic3506
      @milosmilojevic3506 2 месяца назад

      My condolences. It's really hard to progress in this area. There are some promising avenues in the area of immunotherapy but it's early to tell 😢

  • @sofiyaaaaaaaaaa
    @sofiyaaaaaaaaaa 2 месяца назад

    There’s a problem with with the mechanism at 7:38 ain’t it?

    • @totalsynthesis
      @totalsynthesis  2 месяца назад

      Why?

    • @sofiyaaaaaaaaaa
      @sofiyaaaaaaaaaa 2 месяца назад +2

      ⁠@@totalsynthesisbecause you have a carbon lacking in your MeNCO in the second line of the mechanism.So the negative charge on the first cycle attacks the oxygen double bond? Whereas it should attack the electrophilic C=O which poushes C=N pi electrons go on nitrogen which attacks the diazonium
      Ur video is super coool!!!

    • @totalsynthesis
      @totalsynthesis  2 месяца назад +1

      @@sofiyaaaaaaaaaa Thanks! Sorry I still don't get it (maybe because it's 0630 am here). The negative charge attacks the carbon in O=C=N; and the electrons of the C=N bond attack the diazonium. It can be seen as a cycloaddition (what I drew) or a step-wise mechanism

    • @sofiyaaaaaaaaaa
      @sofiyaaaaaaaaaa 2 месяца назад

      @@totalsynthesisyes that’s what I described! It’s just that’s on the second line of mechanism ur reagent is without any carbons ahahah

    • @annadavis2547
      @annadavis2547 2 месяца назад

      This took my father. I am very curious and hopeful for a cure.

  • @lyubomirtrendafilov2684
    @lyubomirtrendafilov2684 2 месяца назад +1

  • @dashingdave2665
    @dashingdave2665 2 месяца назад

    Still, so much research for a cure and, as usual, little work done on the cause.
    Wonder when they will invent a panacea & is that even a realistic idea, from a medical or pharmacological standpoint these days?

  • @HAKIMOSANARQUISTAS
    @HAKIMOSANARQUISTAS 2 месяца назад

    Use cbd and ill put nore on that bet

  • @danaveye3977
    @danaveye3977 2 месяца назад +5

    The neurotoxicity of flourine should be enough to make anyone stop taking SSRIs. Yet here we are trying to repurpose that toxicity. What a time to be alive.

    • @enacherobert1068
      @enacherobert1068 2 месяца назад +17

      what are you talking about?

    • @mobilezeronine2866
      @mobilezeronine2866 2 месяца назад

      ​​@@enacherobert1068there is internet right now, thousands of people brain damaged by psychiatric drugs, antidepressants (prozc) included.

    • @polygon2744
      @polygon2744 2 месяца назад

      @@enacherobert1068 They are talking about fluorine base SSRIs and how fluorine is known to be neurotoxic. Fluoride was found to be neurotoxic and the EPA now must remove it to below neurotoxic levels. The EPA lost a lawsuit where they claimed it was not harmful.