Talk:Tranylcypromine

Changing how much?

I've been trying to fix this article up a bit. However, there's still much to do.

Does anyone mind if I just rewrite the article? Also, what is a useful upper bound to length and complexity? I have a few hundred pages of material that I'd like to know how much to compress ;)

If there's no comment in a reasonable amount of time, I'll assume nobody cares, and go be bold. Zuiram 18:56, 3 October 2006 (UTC)

Hundreds of pages is definitely too much, of course... several pages is often okay, as long as the key info is readily accessible (in summary form) in the opening paragraphs. If you want to put in more, perhaps it's possible to split it into different articles? It would be unusual to have this much info on one drug, but as long as it's encyclopedic, I don't see why not. --Singkong2005 · talk 06:09, 20 November 2006 (UTC)

I definitely agree that hundreds of pages would be too much for an ecyclopaedic article :P

Key information depends on what you're coming to this page for but, yes, I would try to get a reasonable organization for the page; you can have a look at Modafinil, for example, which I refactored to improve the organization and information content. There are very many invalid assumptions and misconceptions about tranylcypromine out there that are not borne out by available research; a game of chinese whispers, if you will; I think Wikipedia should try to stick with what the research supports.

I am not opposed to the idea of splitting the text into seperate articles if it becomes too large to be easily manageable as a single article. Indeed, there are certain topics that clearly deserve their own pages, such as the concomittant use of other medications.

While it is currently unusual for WP articles about a drug to be that extensive, I had been hoping to, over time, add a similar amount of information for most of the antidepressants, except for the SSRIs (which I don't have that much source material for, as the evidence for clinical efficacy can only be described as limited, when compared to other antidepressants).

Your feedback is greatly appreciated, and the reason I'm asking, is that I have a fair bit of info that I'd like to make it possible for others to avail themselves of here, but at the same time, it should conform to the general policies of Wikipedia.

It is a pity that verifiability is the most important criterion here, as that essentially means that some common user feedback (that appears not to have been published primarily because it has become common knowledge among users and prescribers) cannot be part of the article. Npte that I have no problem with writing the article exclusively based on the published evidence; I just disagree with that policy, not going to make a fuss about it.

This drug is an incredibly underestimated drug, and the rarity with which it is currently being prescribed can be clearly attributed to its high cost and the large body of incorrect "knowledge" about the drug that is out there, even among medical professionals. Zuiram 09:30, 21 November 2006 (UTC)

No amphetamine metabolite

Reverted bit about amphetamine metabolite. Respond here before adding it again.

Zuiram 17:04, 29 October 2006 (UTC)

How dangerous is tyramine, for a person taking this drug?

The article says:

Your doctor will provide you with a list of foods to avoid; the most important entries on this list will be the yeast extracts Bovril and Marmite, both of which contain about 100 times lethal amounts of tyramine per serving.

I've added a {{fact}} tag - it's a very serious claim, and I'd like to know if it's true. Sounds as if kissing someone who'd been eating those products could be potentially deadly. --Singkong2005 · talk 06:09, 20 November 2006 (UTC)

Hehe, no, kissing someone who's been eating those products should not be potentially deadly. :)

If you're very sensitive, and they've been painting their lips with it, you might feel it, very weakly, but a single serving is (IIRC) enough to cover a slice of bread or to make a glass of drink. The warning should be heeded, though.

Tranylcypromine potentiates the tyramine pressor response by a dose-dependent factor; a good rule of thumb appears to be a fifty-fold increase or so. Given the interindividual variation in tyramine sensitivity (as well as weight variation; 1 unit BMI increase appears to equate to .84mg TYR30 increase), this means somewhere in the range 4mg-20mg oral tyramine will generally be enough to cause a 30mmHg elevation of systolic blood pressure. The literature frequently states that somewhere in the range 6-10mg oral tyramine is often enough to precipitate a potentially fatal hypertensive crisis.

I seem to have misquoted the number above (100 times), though, as a single serving of Marmite contains "only" about 500-600mg tyramine (IIRC), which about the oral TYR30 for an individual not taking any MAOIs at all. Hence, it's more correct to say 50-100 times the level required to precipitate a potentially fatal crisis.

I don't have the ref in front of me, but I think that either "J Clin Psychiatry 1996, 57: 99-104" or "J. Clin. Psychopharmacol. 1996, 16 (5): 383-388" contains a list of measured tyramine levels for various foodstuffs.

How do you suggest that we rephrase it for now? I think it is important to point out that Marmite and Bovril are about the most dangerous foodstuff you can consume when taking MAOIs, orders of magnitude above anything else that hasn't been spoiled. They are definitely on the "don't eat" list.

Based on the published case reports, such a hypertensive crisis has a fatal outcome in about 62% of the cases, and it would thus be accurate to give an LD50 of about 6-10mg for tyramine.

The talk page doesn't seem to be the ideal place to discuss this (hard to thread, quote etc properly), so if you'd like to take it by mail instead, feel free to do so. Zuiram 09:30, 21 November 2006 (UTC)

I just found a source which gives slightly different numbers for some of these figures. But, notably, it bears out a figure of 625mg tyramine per serving for Marmite. It gives a slightly higher tolerance wrt hypertensive crises at around 10-25mg, which still indicates that Marmite is significantly in excess of a potentially lethal dose. This figure is suspect, though, as other research indicates both great variability and also a lower average figure. We can give an LD50 range of about 4-30mg, depending on the source. I'll have to review my materials to find a more reliable figure (there have been only a handful studies with large-ish numbers of participants, as intentionally provoking a medical emergency is considered ethically dubious). Zuiram 10:26, 21 November 2006 (UTC)

Thanks for all your work, Zuiram. Re taking it to mail - I prefer to discuss it here, as then it's recorded for others to see as well (and it is likely to be useful to other contributors). The quoting and threading take a bit of getting used to but I find it works well (e.g. using : for indents, and <tt>...</tt> for a different font to mark text... or for a more elaborate way of quoting, the {{cquote}} template).

I don't generally have a problem with the quoting methods etc (I used to participate extensively on BBSes back in the day, for instance). It just ends up being a cumbersome amount of text to deal with, especially since reformatting other people's contributions to refactor the discussion into a more systematized form is frowned upon.

If we can agree on mutual refactoring/editing of each others comments for better structure (moving text into subheadings, pruning irrelevant text if it turns stale, etc.), I'd love to have an extensive discussion about what is appropriate for the article or not. Editing the content of the comments is of course not what I'm talking about, just to be clear.

Alternately, we could discuss it on a subpage of one of our userpages or talk pages, and move the relevant parts of the discussion here afterwards, to avoid cluttering up the talk page.

Zuiram 18:15, 6 January 2007 (UTC)

If there are different figures quoted by different sources (which is not surprising, really) then it might be best to say something like "reported LD50s range from 4 to 30 mg" and then supplying a couple of sources... Of course this is assuming the source is notable. Primary sources are usually not suitable (as Wikipedia isn't the ideal place to critically assess researchers' work) so (a) good secondary source(s) that summarizes the results would be ideal. (Actually, the source you quote seems to be a well-written secondary source, so my comment is probably unnecessary.)

Giving the figure as an LD50 would be somewhat misleading, I guess. Somewhere between 4mg and 30mg, depending on individual variations and the degree of MAO inhibition, lies the level at which the rise in blood pressure becomes dangerously high. Of the 80-ish cases (according to one source) where a patient has been admitted to the ER due to a tyramine-induced hypertensive crisis (without other factors like substance abuse), about 50 or so died. I believe the majority of deaths occured in the early years, before proper guidelines for managing the crisis were known.

As for primary vs secondary sources, my experience has been primarily with the primary sources, although I have read several metastudies, synopses, etc... I would say that citing multiple primary sources that say the same thing should qualify the same as citing a single secondary source that has surveyed the primary sources. It is not the same as evaluating the researchers' work, considering the primary sources I use are peer-reviewed studies, whereas many secondary sources have not undergone peer review (I have seen many secondary sources whose advice might be lethal if followed). But I don't know exactly what the official policy on WP is with regards to that; there are several points of official policy I've seen so far that I don't agree with, but I'll try to adhere to them anyway, in the interest of constructive cooperation.

Zuiram 18:15, 6 January 2007 (UTC)

Your rewording seems fair. It's worth putting in citations where available - one of the good things about Wikipedia is that someone who knows the subject has selected the most helpful references. It can be hard for someone who knows little to sift through a google search and decide what to read, where to find the desired info, and which sites to trust.

Yeah, I get that. I'm trying to reassemble the sources I've read for my book on pharmacological treatment of depression now, but it'll take some time. My original interest in researching this material was treatment for my own chronic major depression; I'd been unsuccessfully undergoing treatment for about 8 years or so, and the doctors nearly killed me several times (where knowledge of the research would have made their errors obvious; three times it had been after I had advised against their course of action, with good reason).

I can try to dig up some useful sources, but it'll be quite a bit of work to sift through it again, and my depression is preventing me from working as effectively as I'd like (just switched doctors, and the new one wouldn't continue the treatment that had proven effective, so it's been a few months of progressive worsening now).

Zuiram 18:15, 6 January 2007 (UTC)

I won't do anything on it now, as it's midnight... and probably will do only a little in future, as I'm an engineer with little technical knowledge in this area. But I'll keep watching and help where I can, probably with issues of clarity, giving the lay person's perspective. (Feel free to ask if you need input at all). --Singkong2005 · talk 13:08, 21 November 2006 (UTC)

Hey, I'm not a trained healthcare professional myself. I've just read enough to have a fairly good grasp of antidepressant pharmacology (I've had a pdoc refer a patient to me for advice, and others take my advice to their doctors for a perfect match on the first try). It's complicated, but not as complicated as some people think; it mostly depends on being able to absorb a lot of research and correlate it in a useful manner. Having personal experience with depression also helps a lot (both according to myself, and professionals I've talked to).

And I really prefer to be able to "throw ball" with someone; it almost always gives better results.

Tranylcypromine, and to some extent the other MAOIs, is sort of a pet peeve for me, as it is a fairly complicated drug, but also well studied, and has some pretty impressive results efficacy-wise. However, it is also one of the drugs for which the literature contains a huge amount of cruft; there are many sources that are based on clearly outdated information, misinformation and hearsay. As an engineer (I used to be a software engineer myself), you'd probably label a lot of it as FUD.

So, where should we start in mapping out the right way to proceed with this article?

Zuiram 18:15, 6 January 2007 (UTC)

I also have an interest in this medication, and agree that much of the available information on it is apocryphal, to say the least. A good, well cited entry would be a very positive addition to Wikipedia. FYI, the best book I have found on the MAOIs is the late Dr. Bernstein's *Drug Therapy in Psychiatry* (3rd ed, Mosby, 1995). It would make a good starting point.

The remark about Bovril likely being fatal definitely needs a citation ASAP. The dangers of these foods shouldn't be underestimated, but a remark like that needs more info. I have only seen two documented deaths (in the 1960s) attributed to tyramine reactions.

Info on the treatment of hypertensive crises (gold standard is the alpha blocker phentolamine administered IV), and the major drug reactions cocaine, certain narcotics, and SSRI's (SSRI+MAOI's=serotonin syndrome--far more likely to cause death than a tyramine reaction) is also important.

If you like, I can add some of these details with citations when I have time.

BR,

Dave David A. Flory 15:01, 31 January 2007 (UTC)

The validity of the analogues section

I have added a new section on the WT:PHARMMOS page [1] for all those interested in having their say. Brenton (contribs · email · talk · uploads) 11:04, 5 October 2014 (UTC)

I don't think it is appropriate or particularly helpful without any accompanying discussion/explanation/context, so I have removed it. I'm placing the references here in case anyone would like to use them to write some actual text about tranylcypromine analogs. -- Ed (Edgar181) 14:16, 9 October 2014 (UTC)

1. Kaiser, C.; Lester, B. M.; Zirkle, C. L.; Burger, A.; Davis, C. S.; Delia, T. J.; Zirngibl, L. (1962). "2-Substituted Cyclopropylamines. I. Derivatives and Analogs of 2-Phenylcyclopropylamine". Journal of Medicinal and Pharmaceutical Chemistry. 5 (6): 1243. doi:10.1021/jm01241a017.
2. Zirkle, C. L.; Kaiser, C.; Tedeschi, D. H.; Tedeschi, R. E.; Burger, A. (1962). "2-Substituted Cyclopropylamines. II. Effect of Structure upon Monoamine Oxidase-Inhibitory Activity as Measuredin Vivoby Potentiation of Tryptamine Convulsions". Journal of Medicinal and Pharmaceutical Chemistry. 5 (6): 1265. doi:10.1021/jm01241a018.
3. Cho, S. J.; Jensen, N. H.; Kurome, T.; Kadari, S.; Manzano, M. L.; Malberg, J. E.; Caldarone, B.; Roth, B. L.; Kozikowski, A. P. (2009). "Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action". Journal of Medicinal Chemistry. 52 (7): 1885–902. doi:10.1021/jm801354e. PMC 2832311. PMID 19284718.

Substrate or Inhibitor?

Just to clarify, TCP acts as an inhibitor for those CYP450 enzymes (CYP2A6, CYP2C19, CYP2D6) and is not necessarily a substrate of any of them. I have found no evidence to prove otherwise, and I've done some digging. I went ahead and fixed the language in that section. — Preceding unsigned comment added by 68.185.202.126 (talk) 17:24, 17 April 2016 (UTC)

There's directly conflicting information in this article about it not inhibiting any enzymes and being ONLY a substrate of CYP2D6, and then it says it's an inhibitor. 75.97.104.73 (talk) 12:03, 5 May 2023 (UTC)