Withdrawn drugs

[HeadphonesandLSD]

I ended up on this page at wikipedia tonight: https://en.wikipedia.org/wiki/List_of_withdrawn_drugs

I was wondering if you guys knew of any substances that were withdrawn from the market and hopeful you might have something to say about them. Going through that list is very interesting. I am surprised that so many were used for about a year then pulled for cases of early deaths or organ damage. One of the first results is this odd ball z-drug I've never heard of that was poised to become a replacement for xanax: https://en.wikipedia.org/wiki/Alpidem but it was taken off the market for causing liver damage.

 

[Anonymous Dissident]

I used to enjoy propoxyphene (on very rare occasions), but I believe it was withdrawn from use due to Q-t elongation. It's too bad, I dont enjoy many painkillers and this was one of the rare exceptions. That's the only withdrawn drug I have any significant experience with.

 

[fm3]

I think you can count on it being a common practice in the pharmaceutical industry for rival companies to fund university research studies aimed at finding anything at all that might damage the reputation of a competitor's successfully brought to market under exclusive patent-protection pharmaceutical drug.

How many of these recalled drugs have been done so solely on the basis of findings in animal models? Every one that has been on the market has gone through a process that includes extensive human trials in order to be approved, and yet all it takes to reverse this process is the work of a few 'researchers' forcibly inducing negative conditions in a non-human animal with a chemical that if history teaches us anything may very well not have been the one they were supposed to be using anyway. Like that one study into the neurotoxicity of MDMA that was published before somebody found out they were so fucking dumb that they thought Methamphetamine was the same thing as MDMA.

These guys are always making their own testing standards for these experiments for 'some reason' now that I think about it.

 

[izo]

i had some dexfenfluramine years ago, it was nice and although an amphetamine didnt feel like one. it would make you calm and relaxed but without any of the stimulating effects of for example mdma.

 

[Rectify]

Bad for heart valves. Substitute N-ethyl-3-methylamphetamine for fenfluramine. Nasty teflon 3-Ar-CF3's.

 

[Skorpio]

I think you can count on it being a common practice in the pharmaceutical industry for rival companies to fund university research studies aimed at finding anything at all that might damage the reputation of a competitor's successfully brought to market under exclusive patent-protection pharmaceutical drug.

How many of these recalled drugs have been done so solely on the basis of findings in animal models? Every one that has been on the market has gone through a process that includes extensive human trials in order to be approved, and yet all it takes to reverse this process is the work of a few 'researchers' forcibly inducing negative conditions in a non-human animal with a chemical that if history teaches us anything may very well not have been the one they were supposed to be using anyway. Like that one study into the neurotoxicity of MDMA that was published before somebody found out they were so fucking dumb that they thought Methamphetamine was the same thing as MDMA.

These guys are always making their own testing standards for these experiments for 'some reason' now that I think about it.

Please cite evidence of this before making such a sweeping conclusion. Most of these drugs were withdrawn after serious adverse events occured (like beyond slapping a black box warning on the drug).

See fenfluramine, propoxyphene (which prolonged qt so much that it was the go to drug that right to die groups would reccomend overdosing on for euthanasia (after pentobarbital became hard to get because it was withdrawn)), phenacetin... just read the list and look for a single thing that was withdrawn due to an animal study.

 

[Cotcha Yankinov]

I think you can count on it being a common practice in the pharmaceutical industry for rival companies to fund university research studies aimed at finding anything at all that might damage the reputation of a competitor's successfully brought to market under exclusive patent-protection pharmaceutical drug.
--
Like that one study into the neurotoxicity of MDMA that was published before somebody found out they were so fucking dumb that they thought Methamphetamine was the same thing as MDMA.

If we wanted to put on tinfoil hats you could say that the DEA swapped the MDMA for METH on purpose. I believe Ricaurte repeatedly expressed that the results needed to replicated by other labs and that those types of effects on dopamine neurons had never been seen before. He of course immediately retracted his paper when he learned the truth. As far as I can tell, he was just a researcher who cared about neurodegenerative disease, and pushing MDMA to neurotoxic levels in animals is a useful way to study neurodegeneration, in case his reputation still needs any defending..

I think it highlights the need for results to be verifiable by other groups. See Philip Seeman and his love for finding D2 affinity on everything, even for Eli Lily's group 2/3 metabotropic glutamate agonist. Other labs could not replicate that result and many of his other results, not that there would be much of a vested interest therein. IIRC some of the research done after that showed that Eli LIly's compound didn't show efficacy particularly in patients who had already had long term exposure to AAPs (their 5-HT2A antagonism seemed to have caused genetic effects that decreased the LY compound's efficacy). Obviously something that could not be seen in animal models, so I certainly agree that thorough human studies are important.

I'm sure an industry insider could tell you more about intellectual warfare between pharmaceutical companies but its hard to bend results that much in the scientific arena without somebody calling BS eventually. I don't think some of the more serious side effects of anti-epileptics (like SJS and TENS) were really well known until post-marketing surveillance, but my memory could be fuzzy there. 1 in 1300 is pretty rare, you could definitely have a 1000 patient trial and miss it. And then you have Japan that goes straight from phase III into post marketing surveillance IIRC.

Not exactly a drug withdrawn off the market, but another case of humans showing vastly different results than animals, this catastrophic trial
https://en.wikipedia.org/wiki/BIA_10-2474

 

[Anonymous Dissident]

If we wanted to put on tinfoil hats you could say that the DEA swapped the MDMA for METH on purpose. I believe Ricaurte repeatedly expressed that the results needed to replicated by other labs and that those types of effects on dopamine neurons had never been seen before. He of course immediately retracted his paper when he learned the truth. As far as I can tell, he was just a researcher who cared about neurodegenerative disease, and pushing MDMA to neurotoxic levels in animals is a useful way to study neurodegeneration, in case his reputation still needs any defending..

I think it highlights the need for results to be verifiable by other groups. See Philip Seeman and his love for finding D2 agonism on everything, even for Eli Lily's group 2/3 metabotropic glutamate agonist. Other labs could not replicate that result and many of his other results, not that there would be much of a vested interest therein. IIRC some of the research done after that showed that Eli LIly's compound didn't show efficacy particularly in patients who had already had long term exposure to AAPs (their 5-HT2A antagonism seemed to have caused genetic effects that decreased the LY compound's efficacy). Obviously something that could not be seen in animal models, so I certainly agree that thorough human studies are important.

I'm sure an industry insider could tell you more about intellectual warfare between pharmaceutical companies but its hard to bend results that much in the scientific arena without somebody calling BS eventually. I don't think some of the more serious side effects of anti-epileptics (like SJS and TENS) were really well known until post-marketing surveillance, but my memory could be fuzzy there. 1 in 1300 is pretty rare, you could definitely have a 1000 patient trial and miss it. And then you have Japan that goes straight from phase III into post marketing surveillance IIRC.

Not exactly a drug withdrawn off the market, but another case of humans showing vastly different results than animals, this catastrophic trial
https://en.wikipedia.org/wiki/BIA_10-2474

Wow, I hadn't seen that before. I'm glad I've passed on other FAAH inhibitors that have been sold as rc's. I know a single chemical can't really be predictive for an entire class, and other FAAH inhibitors haven't shown similar neurotoxicity, but I'll happily sit on the sideline and let others play lab rat with these...

 

[fastandbulbous]

Thalidomide - sedative to reduce morning sickness.

Need I say more?

 

[plumbus-nine]

Pemoline is said to have been a good stim and possibly superior to amphetamine. Prolintane (ex katovit) was nice too. And in the European Union kava kava.

 

[Nas47]

Pemoline is said to have been a good stim and possibly superior to amphetamine. Prolintane (ex katovit) was nice too. And in the European Union kava kava.

Methaqualone is withdrawn in most countries,LAAM(long acting agent for opioid substitution.....many