Talk:Sunifiram

Side effect of chronic headaches

Word to the wise - be aware that numerous users have reported pressure headaches, often lasting weeks or even indefinitely in one case from the use of sunifiram in combination with other agents. The symptoms may likely include tinnitus and worsening of sleep. Of concern is the fact that it was the addition of sunifiram that initiated the symptoms. This information was removed from the article because it was not backed up by a scientific article, but it nevertheless ought to be of significant concern. --IO Device (talk) 07:21, 25 November 2013 (UTC)

Removed section contents: Safety

OK, this speculation has got to stop. Can we please keep this page factual? I.E. anything not demonstrated by a study does not belong here. I see absolutely nothing unreasonable about what I am proposing but do see what people like IO_Device are adding to the page as damaging. 2.30.51.94 (talk) 13:54, 20 June 2013 (UTC)

Your claim of "speculation" is bogus because no speculation was ever added to the Safety section. Each statement there was well sourced, and is validated by multiple journal articles and studies. No one said or even suggested that sunifiram causes excitotoxicity or cancer. The facts were presented simply as they are. Since you are not familiar with editing Wikipedia, I will advise you that it is completely normal for related statements to be presented in an article, as long as they're referenced and are presented neutrally. The fact that you don't like a particular statement is not an acceptable reason to remove it. I know you will disagree, but before you do, I advise you to consult a Wikipedia administrator. Why do you think that having safety related information is damaging? Because you have been basically censoring the article, which is a peculiar thing to do, it is required that you declare your financial connections to sunifiram. You have 24 hours, after which the content will be reinserted into the article. --IO Device (talk) 16:26, 20 June 2013 (UTC)

I'm the DRN volunteer who closed the request there for lack of talk page discussion. I do want to comment on this matter, however. I've not looked back through all the reverts, but am going to assume that this edit encapsulates the issue. I have to agree that the material should not be included in the article, not due to lack of sourcing, but because its inclusion violates the WP:SYNTHESIS section of the No Original Research policy, which says:

"Do not combine material from multiple sources to reach or imply a conclusion not explicitly stated by any of the sources."

(Emphasis added.) This information is clearly being included to imply or suggest that there safety issues connected with Sunifiram, but the deleted material only says that there are safety issues connected with PKC alpha. Unless the sources in the removed material specifically discuss Sunifiram, then to suggest or imply that there are safety issues with Sunifiram because it activates PKC alpha and there are safety issues with PKC alpha is prohibited original research via implication under Wikipedia policy. Even if that is not the intent of the editor who wishes for it to be included, it clearly has that effect and appearance and is improper for that reason. Regards, TransporterMan (TALK) 14:53, 21 June 2013 (UTC)

PS: At the DRN listing IO Device said, "As with any drug, readers are very interested in knowing any possible safety concerns. The removal of these concerns by 2.30.51.94 potentially places the readers in jeopardy if they, in their ignorance, choose to use the drug." It is a well-established principle that Wikipedia is not a soapbox and does not raise or imply safety issues which have not specifically been first raised in reliable sources. — TransporterMan (TALK) 15:14, 21 June 2013 (UTC)

For the record, the removed content is saved below, in case more appropriate evidence presents itself in the future. --IO Device (talk) 16:41, 21 June 2013 (UTC)

Safety

Overactivation of glutamate receptors, especially NMDA but also AMPA receptors, induces excitotoxic neurotoxicity.

Sunifiram, like galantamine, activates PKC-α. PKC-α activation has various cellular functions, and can enhance learning and memory. Increased activation of PKC-α is also associated with the growth and invasion of cancers. High levels of PKCα are linked to malignant brain cancer. Moreover, a high proliferation rate of glioma tumor cells is the result of overexpression of isozyme PKC-α.

References

Ampakine or not?

I think the AMPA PAM claim, considering it's uncited, must not be kept in the article. I find there is inadequate substantiation thus far for an allosteric effect. --IO Device (talk) 22:31, 21 June 2013 (UTC)

Doi 10.1111/j.1527-3458.2006.00039.x clearly hypothesizes ampakine modulation. E.g. p.46: "NBQX, inactive on its own, antagonizes the unifiram reversal of the KYNA antagonism of the NMDA-evoked tritium release (Fig. 4A) as well as the sunifiram-mediated effect (Fig. 4B), suggesting involvement of AMPA receptors in the effects of both compounds (11)". Also p.49: "The hypothesis that unifiram and sunifiram exert their antiamnesic effect through the activation of AMPA-mediated effects is also supported by in vitro results in which both compounds produced a NBQX-sensitive reversal of the kynurenate-induced antagonism in the 'kynurenate test.'" I have therefore restored the cut text but have added "appears to" with the reference. — Preceding unsigned comment added by GKantaris (talk • contribs) 06:43, 24 June 2013 (UTC)

Replying to your deleted comments:

There are two things you need to know: 1. Ampakine requires ALLOSTERIC modulation. Until you find a sourced statement stating that sunifiram is allosteric in its effect, or until you show a direct sourced statement that sunifiram is an ampakine, you cannot call it an ampakine. 2. An agonist doesn't have to be allosteric. --IO Device (talk) 07:01, 24 June 2013 (UTC)

You're the one deleting things and adding things without evidence (like all the stuff about Sunifiram and cancer), and generally impoverishing and damaging the article. A number of the careful studies undertaken by Galeotti and team show "AMPA-mediated" effects. Sure, the word "allosteric" isn't used by that team, but they're showing indirect AMPA activation, not claiming direct binding to receptors. The statement that sunifiram is a PAM of AMPA has been in the article from before you were involved in editing it. You coming in and just removing it needs a bit more research and sifting through evidence than you seem to have done. And try to keep things civilized -- accusing me of being "lame" because I tried in a bit of a hurry to *restore* content you arbitrarily deleted (you've never made a typo, huh?) and threatening to "report" me because you don't see the evidence I see in the article I read and cited in good faith (i.e. over a matter of interpretation), suggests you're getting unhealthily possessive about this article. GKantaris (talk) 10:22, 25 June 2013 (UTC)

Why would you reply to my deleted comments? Clearly I deleted them for a reason, i.e. I didn't mean them. Are you feeling sane? I am not stopping anyone from making sourced, relevant, and constructive edits to the article. For now, all I am saying is that I too have read the reference, and it does not say that sunifiram is a PAM, yet you continue to lie about it. I acknowledge that it is a dirty ampakine (dirty in that it also affects NMDAR activation). In your comment above, you also lied about me linking sunifiram and cancer. The truth is that I only linked PKCa and cancer. Let's move on and continue to improve the article with justified claims. --IO Device (talk) 17:03, 25 June 2013 (UTC)

Removed section: Alternatives

The section quoted below was removed by an editor. It is saved here.

Alternatives

Nefiracetam is a drug with similar effects. Lithium potentiates AMPAR and LTP while inactivating Src kinase and protecting against NMDAR excitotoxicity.

References

--IO Device (talk) 15:47, 24 September 2014 (UTC)

Sources

• There is a box at the top of this page with a link to reviews in the biomedical literature. this is the search and there are no results.
• search of the NY Times has no results.
• search of WSJ yields nothing.
• CDC search - nothing
• google books - nothing but a couple of passing mentions in poor quality books

What are the reliable sources about this compound?

I think it fails WP:NOTABILITY and probably should be deleted... Jytdog (talk) 00:36, 8 February 2016 (UTC)

The compound has been sold and discussed heavily online for the past few years. It has destroyed the lives of many people too, for reasons not limited to drug interactions causing lasting brain damage. The safety section is already significantly watered down. Deleting the article or removing mention of its safety section will only promote ignorance of it. The recently added reference by Aethyta about it being sold online may qualify as a secondary source for the compound. --Hyperforin (talk) 00:41, 8 February 2016 (UTC)

Yet you reverted my edit that it's 1.) a nootropic and 2.) being sold as a designer drug? I don't understand your reasoning behind this. Also do you have any sources for your post above, brain damage? Aethyta (talk) 00:44, 8 February 2016 (UTC)

Aethyta if you look at the content you added, both the content and the source were already in the article. Your addition of the wikilink to designer drug was good, but the rest was redundant. Hyperforin fixed that. Jytdog (talk) 00:47, 8 February 2016 (UTC)

Aethyta, if you have a secondary source reference with appropriately quoted text to clearly suggest that the drug is a nootropic and a designer drug, then the inclusion of those terms is fine by me. As for brain damage, please feel encouraged to search Longecity and Reddit for user reviews discussing lasting neurological symptoms from sunifiram. I have messages in my Longecity inbox from a half dozen users complaining of the same. Really though, what part of NMDAr excitotoxicity is difficult for you to understand? I need not provide you with journal references for the same because I haven't added the claim of brain damage to the article itself. --Hyperforin (talk) 01:36, 8 February 2016 (UTC)

Hyperforin I understand very well that you are passionate about this. Please know that Wikipedia is not a vehicle for advocacy by anybody (See WP:PROMO which is policy and please see the helpful essay section that explains that policy some, WP:RGW and also the other helpful essay that explains that policy some, WP:ADVOCACY. Again I am not questioning your motives to help the world at all. I am saying that Wikipedia's policies and guidelines govern what we do here in WP. Above I was addressing the WP:NOTABILITY policy; that does need to be addressed. Please do reflect on all this. Thanks. Jytdog (talk) 00:50, 8 February 2016 (UTC)

Jytdog, as far as I'm concerned, the drug is genuinely notable because it has been consumed and discussed for years in nootropic circles. Moreover, I already noted that Aethyta provided a secondary source which should help establish the notability of the drug. I am certainly not trying to promote usage of the drug. I actually don't care about any of the edits you made to the Mechanisms section for that matter. The Safety section was actually very mildly written; it had no controversial claims. I don't understand why you removed it but it really doesn't matter; I'll fight you to the end of the world for keeping it so long as the article exists. Please prepare yourself to monitor this article everyday for the rest of time. I have tens of thousands of dollars to spare on international VPNs that are not blocked by Wikipedia. Up until now I have respected you a lot, but in this case I'll actually turn vindictive in my various edits if you persist in deleting the section. It'll be a total lose-lose scenario. --Hyperforin (talk) 01:42, 8 February 2016 (UTC)

two quick replies. first I never said that you were trying to promote it - I get it that you want to protect people. Second, the last statements you wrote there show that what you care about, is not editing according to Wikipedia's policies and guidelines, but rather what is important to you. and that you are willing to do crazy stuff to get what you want. I suggest you strike them. Those statements alone are enough to get you site-banned. I know you are angry and apparently getting angrier. That is not helpful to WP but especially not to you. Again, please strike that (like this) and then go take a break and reflect on what WIkipedia's policies and guidelines actually say, and more importantly their spirit. Please. Jytdog (talk) 01:55, 8 February 2016 (UTC)

First Nuklear, now this. Oh well, page protection would do the trick. Aethyta (talk) 02:03, 8 February 2016 (UTC)

Aethyta, Are you kidding me? Unless the page is restricted to be edited by Administrators only, it'll take me no time at all to establish a new/established account and return here. Please do not confuse me with some dumb anonymous troll. --Hyperforin (talk) 02:08, 8 February 2016 (UTC)

Jytdog, I am actually a fairly productive Wikipedia editor, with many more good, dispassionate, and uncontroversial edits to come in the near future on some very significant topics. It would be pretty harmful for Wikipedia to lose me as an editor on account of this article alone. Yes, it's damn right that I want to protect people. The Safety section as it was written has a direct impact on saving people from brain damage. I know of first-hand accounts of users who thoughtfully refrained from using the drug after they read the section. I guess you will never understand because these are all just bureaucratic abstractions to you - you don't actually know what it means for people to suffer the consequences from the drug. I am not striking anything. I suggest you undo your edit immediately. Like I said, there was nothing in the Safety section that was actually controversial. --Hyperforin (talk) 02:05, 8 February 2016 (UTC)

You are not acting like a productive editor and if this is what you do when you get angry, your future here is dark and promises to be brief. Not long and not useful. Again, calm down. And stop personalizing this. I will give you a last chance to strike what you wrote above. If you don't I will bring you to ANI and you will be site banned. What you wrote there is unacceptable (and you know that if you are an experienced editor). By the way, I am reading the Gualtieri paper but your angry responses are stopping me from working. Jytdog (talk) 02:08, 8 February 2016 (UTC)

Jytdog, I am not sure what it is exactly that you want me to strike. Please clarify. I'll strike or remove it if it makes you happy, but does that mean I didn't mean what I said? It's actually you who are taking this personally with your repeated reverts. You never presented any good explanation for removing the Safety section. --Hyperforin (talk) 02:11, 8 February 2016 (UTC)

Your behavior has become the focus of the discussion. The following are bann-able statements:

• All the stuff beginning with "I will fight you to the end of the world..." to the end of that comment. (the one date stamped 01:42, 8 February 2016)
• Everything after "Are you kidding me?" in the next comment
• The stuff beginning with "I guess you will never understand because these...." to the end of that statement is over the line but not as bad as the stuff above, I suggest you strike it too.

You strike by putting <s> in front and this </s> at the end.

I am trying to finish reading the Gualtieri paper. Jytdog (talk) 02:19, 8 February 2016 (UTC)

OK i finished reading the paper. It has not yet been classified by Pubmed nor MEDLINE but my guess is that they will classify it as a review, so it is a secondary source. It is not however independent since it is a review of Gualtieri's own work (as well as some work others have done with his compound). So the first thing I did was just to stubify the article, making just high level statements based on that one kind-of-good source. With only that to go on we should not go into all the detail that was there. Gualtieri was very clear that the drug has not been through tox testing, has not been in human trials, and is not approved for sale anywhere in the world. (The question you had about the safety section is moot now, but it had unsourced content in it, and the statement that was there was not supportable with the source that was provided) I don't think we should go into the whole availability on the internet, per WP:BEAN. I am debating whether to put this up for deletion as it fails WP:Golden rule (which is just a nice, high level summary of WP:NOTABILITY. Not sure yet. Aethyta what are your thoughts on all this? Jytdog (talk) 02:43, 8 February 2016 (UTC)

That could be said about every drug article ever. If something exists, it's worth writing about; no reason to play moral police. Prohibition doesn't work, as opposed to education.Aethyta (talk) 03:56, 8 February 2016 (UTC)

Hyperforin I struck part of what you missed. If that is not OK please revert me but for your sake I suggest that you don't. Jytdog (talk) 02:45, 8 February 2016 (UTC)

Despite your sound logic, I advise against nominating it for deletion because that will result in a loss of safety information for the article. It is already bad enough that the link to PKC alpha#Pathology no longer exists in the article - it is essentially what kept readers from using the drug, and now it's gone. I attribute future incidences of brain damage by sunifiram to this change. --Hyperforin (talk) 03:05, 8 February 2016 (UTC)

The claim that this chemical acts activates PKCalpha was indeed in PMID 23733502 but the rest of that sentence, that this "may present safety concerns of its own." was unsourced. That source doesn't say it. The Gualtieri review briefly mentions PKC activation (one sentence) but also says nothing about pathology. That sentence failed WP:VERIFY and appears to be original research which is not allowed in WP. I do understand your concern but you appear to be trying to make Wikipedia that into something it is not. All three of those links are to policy btw. Jytdog (talk) 03:13, 8 February 2016 (UTC)

Oh there exist plenty of references to show that PKC activation is associated with pathologies. I just don't know if you'd want me to include them in this article. Why is it then such a stretch to say that "Sunifiram activates PKC alpha and this presents safety concerns"? — Preceding unsigned comment added by Hyperforin (talk • contribs) 03:32, 8 February 2016‎ (UTC)

No please don't do that -please read WP:SYN. Oh, and by the way, about your penultimate comment -- at the bottom of every Wikipedia page, in tiny print, you will find a link called "Disclaimers". Please click on that and then click on the "Medical Disclaimer" in the header there. Jytdog (talk) 03:48, 8 February 2016 (UTC)

How about, "Sunifiram activates PKC alpha. Activation of PKC alpha is associated with cancer." What's wrong with that? I don't take it as a violation of SYN since both statements will be independently verifiable. Please realize that this statement will make or break the difference between whether a reader uses the drug or not. --Hyperforin (talk) 04:52, 8 February 2016 (UTC)

WP:SYN is doing exactly what you are doing - putting two statements together to make a claim about this chemical that are no where said about this chemical. That is exactly what SYN (which is policy) is meant to prevent. It became policy like all policies came into being - because lots of people have wanted to add original research in exactly that way, and OR is OR is OR. (step back and think about all the invented garbage you could add to Wikipedia, doing just that kind of juxtaposition) Jytdog (talk) 05:55, 8 February 2016 (UTC)

You have made it extremely clear that you want to add this content to WP because you believe it will save people's lives. Please stop repeating it. That is not what Wikipedia is for.. I cannot tell you how many people come to Wikipedia and demand to add garbage content because It Is Very Important To Save Lives And It is True. I had somebody battle and attack me about a day (before they were finally banned) about how some herb cures cancer. That was also Very Important To Save Lives And Was True. No reliable sources for it, of course. But it was True. We have policies and guidelines not because we are bureaucratic morons, but because the same problems arise over and over and over, especially with new editors who come here very very passionate about something.

The mission of WP is to provide people with "accepted knowledge". We have literally nothing to say to people want to buy chemicals off the internet and ingest them. (I would have plenty to say in person if I met someone like that at a bar, but that is another matter) Here content must be verified with a reliable source that itself transmits accepted knowledge. Jytdog (talk) 06:01, 8 February 2016 (UTC)

For the record, there is a fundamental difference between promoting an agent and highlighting its safety concerns. The two are not the same. I tend to set the bar low for references for the latter. You'll never see me go this far to promote an agent. I'm tired of hearing of the restricted mission of WP. If you survey random readers of the article if WP should highlight safety concerns even if they're synthesized, I bet that a large percentage would favor it. This is because safety is paramount, and SYN is not.
I'll go so far as to say that you're quite the hypocrite for selective application of SYN - your friends Some users on Wikipedia very often add notices effectively saying that "this substance is not proven to treat any disease" even though making such a claim very clearly falls under SYN, and is potentially incorrect as well. --Hyperforin (talk) 13:36, 8 February 2016 (UTC)

You haven't said anything new here about content. I will reply about the other things on your Talk page which is more appropriate for that. Jytdog (talk) 02:34, 9 February 2016 (UTC)

Chemical structure contradiction

The journal article here refers to sunifiram as "novel pyrrolidone nootropic drug sunifiram". If sunifiram is indeed a pyrrolidone, then the chemical structure presented in the article here is incorrect. ChemNerd (talk) 18:06, 11 March 2016 (UTC)