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

[@totalsynthesis]

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]

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

[@squareacid]

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

[@bushhawk5460]

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

[@some_haqr]

Ah man i fucking hope so now dude

[@Fiberoptic11]

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]

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

[@fatman9644]

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]

Yes spot on. Nice profile pic 😂

[@-r-495]

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]

Thanks!

[@Lock484]

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]

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 😓.

[@chemistrycapital]

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.

[@chemistryofquestionablequa6252]

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]

you're missing out.

[@chemistryofquestionablequa6252]

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

[@timecode37]

@@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]

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

[@danaveye3977]

@@chemistryofquestionablequa6252 SSRIs are neurotoxic. End of story

[@OsmioIridio-og8cn]

Excellent content

[@totalsynthesis]

Thanks Giga Chad!

[@martinperales3531]

Love the coverage of the biology aspects, great

[@totalsynthesis]

Glad you liked it!

[@dariusszablowski5474]

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

[@totalsynthesis]

Why mixed up?

[@MandrakeFernflower]

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

[@stevengill1736]

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...

[@Geneu97]

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

[@TheBackyardChemist]

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.

[@jhonbus]

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!

[@totalsynthesis]

1000%

[@nostro1940]

Not everyone is 150 lQ like you

[@andreasholmqvist4422]

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

[@totalsynthesis]

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

[@abs0lute-zer061]

I actually got this one on time!

[@totalsynthesis]

Yasss

[@geekswithfeet9137]

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

[@totalsynthesis]

Never feel too safe around that many nitrogens

[@Psychx_]

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.

[@johnthomas2970]

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

[@lilianparle4822]

On telegram.

[@kenhaze5230]

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.

[@totalsynthesis]

Hahah I swear

[@acidangel162]

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]

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

[@jairo8746]

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]

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

[@totalsynthesis]

For real

[@isa-manuelaalbrecht2951]

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

[@williammcghee863]

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

[@totalsynthesis]

Oh man... my condolences

[@milosmilojevic3506]

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]

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

[@totalsynthesis]

Why?

[@sofiyaaaaaaaaaa]

⁠@@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]

@@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]

@@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]

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

[@lyubomirtrendafilov2684]

❤

[@dashingdave2665]

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?

[@grdfhrghrggrtwqqu]

How TMZ is an experimental chemistry related publication is beyond me. This is even worse than the biologists that use tiktok.

[@HAKIMOSANARQUISTAS]

Use cbd and ill put nore on that bet

[@danaveye3977]

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]

what are you talking about?

[@mobilezeronine2866]

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

[@polygon2744]

@@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.