The following discussion is an archived debate of the proposed deletion of the article below. Please do not modify it. Subsequent comments should be made on the appropriate discussion page (such as the article's talk page or in a deletion review). No further edits should be made to this page.

The result was keep. (non-admin closure) Peter Karlsen (talk) 01:30, 1 November 2010 (UTC)[reply]

Substituted phenethylamines

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Substituted phenethylamines (edit | talk | history | protect | delete | links | watch | logs | views) – (View log) • Afd statistics
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notability: no unambiguous definition provided in literature; definition requires extrapolation from various sources which may conflict depend on intent of source; term is used in scientific literature for convenience and not as a topic of discussion in itself

The content is unverifiable or the underlying concept is non-notable, The list is unlimited and/or unmaintainable, The list has no content beyond links to other articles, so would be better implemented as a (self-maintaining) category, The list is unencyclopaedic, i.e. it would not be expected to be included in an encyclopaedia, Determining membership of the list requires adoption of a non-neutral point of view and reliable sources for avoiding it are not available. Determining membership of the list involves original research or synthesis of ideas.

I'm relatively new to actually editing wikipedia, so I added the above after writing my reasons, which I'll keep, below:

I don't believe the subject warrants its own article largely because there is no "official" definition of a "substituted phenethylamine." You can find the terminology used in scientific literature, but the definition of a "substituted phenethylamine" is going to be in the eye of the beholder. For example, in Alex Shulgin's Phenethylamines I Have Known and Loved, his criteria for inclusion is based on the synthetic process used to make a drug, his intent to explore derivations of the phenethylamine moiety and the limitations in the number of substances he synthesized (if he'd produce 10000 for the book, dextrorphan could have been included in PIHKAL). I can find scientific research articles pointing out that, for example, opioids (including heroin) contain the phenethylamine moiety and thus could be considered "substituted phenethylamines." Similarly, LSD even contains the phenethylamine moiety embedded in it. PIHKAL doesn't offer a good definition of what phenethylamines are, except for compounds with "appropriate" substitutions to the backbone.

In patents referring to a "substituted phenethylamine" the definition depends on the intentions of the invention. US patent 20070148622, titled "Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity" includes a definition of "substituted phenethylamines" that is very different than the image on wikipedia's substituted phenethylamines page.

Underneath the image on the wikipedia page the caption states that the formula is the "basis of all substituted phenethylamines" but this contradicts other sources, such as the patent I mentioned which considers venlafaxine (Effexor) to be a "substituted phenethylamine". While the wiki article on venlafaxine calls it a "phenethylamine," venlafaxine is not mentioned on the list of substituted phenethylamines.

Now, maybe one could make an argument that "substituted phenethylamines" are notable due to Shulgin's book, but I also see that there are entries for "substituted amphetamines" and "substituted methylenedioxyphenethylamines." This is just ridiculous because there is a lot of overlap between these groups: the difference between phenethylamine and amphetamine is only ONE methyl group. We could easily come up with an arbitrarily large number of "substituted (whatevers)" and end up listing most of the same chemicals over and over in these groups. The list of substituted amphetamines, for example, should have very large overlap with "substituted phenethylamines."

That's part of my question then, is why is there a list, for "substituted phenethylamines" and not for "substituted (any other arbitrary moiety)?" Why no substituted methanes?

I'd like to reiterate that even though you can find the term "phenethylamine" (and "substituted phenethylamine") being used in scientific literature to discuss various structurally related compounds, how the term is used or defined also depends on the subject matter of the article and who the article is written for (biologists may define a "phenethylamine" in a paper one way while a medicinal chemist may define the term another way). The term is used in science literature for convenience because the phenethylamine moiety is quite ubiquitous, but I challenge anyone to find a source providing an unambiguous definition (you won't). There's no, one, unambiguous definition for "substituted phenethylamines." It's a convenient term to use when the subject matter at hand is a bunch of related compounds. I tentative plan to make the same proposal that "substituted amphetamines," "substituted methylenedioxyphenethylamines" be deleted.

I assert that the "substituted phenethylamine" article does not meet the notability guideline: "Significant coverage" means that sources address the subject directly in detail, so no original research is needed to extract the content. Significant coverage is more than a trivial mention but it need not be the main topic of the source material." AlkaloidMan (talk) 10:29, 25 October 2010 (UTC)AlkaloidMan[reply]

comment
When it comes to innovative ways of navigative chemicals, shouldn't those ways at least be sensible? Instead of using vaguely defined groups, shouldn't we at least make sure that the lists are sensible and try to eliminate lists that have a ridiculous amount of potential overlap?
Why not reorganize the categories into something verifiable? For example, instead of vague classes like "substituted phenethylamines (PEAs)" "substituted amphetamines" and "substituted methylenedioxyphenethylamines," why not reorganize into categories like "phenethylamine derivatives with adrenergic activity" (and eliminate the largely overlapping subgroups like "substituted amphetamines" and "substituted methylenedioxyphenethylamines"?) As a pharmaceutical chemist, wouldn't you find it far more sensible to use the moiety that encompasses the largest number of these compounds (i.e. keep substituted phenethylamines and eliminate substituted amphetamines and substituted methylenedioxyphenethylamines) and then reorganize the substituted phenethylamine group into categories like "PEA derivatives with adrenergic activity", "PEA derivatives with serotonergic activity."
The way the category is defined now is wholly arbitrary. I don't see any reason why we couldn't include benzomorphans, morphinans, morphine and related compounds, 1,2,3,4-tetrahydroisoquinoline and its derivatives, ergot alkaloids, and ANYTHING else with a PEA moiety in it. The category needs to be defined better than just "substituted PEAs" because that encompasses a potentially infinite number of compounds.
I can find a bunch of articles discussing the phenethylamine moiety in these structurally more complex molecules. For example, Bird et al. (1976) discuss the orientation of phenethylamine in dexclamol and apomorphine. The article/list either needs to be re-written and re-categorized so that it makes sense, because an article JUST about substituted PEAs doesn't tell us anything. Substituted PEAs by pharmacological activity on the other hand does make sense. However, even if the categories are reorganized that way, then we should eliminate the redundancy by getting rid of "substituted amphetamines" and "substituted 3,4-methylenedioxyphenethylamines" pages and including enough information to allow someone to infer which compounds would also be substituted amphetamines or substituted 3,4-methylenedioxyphenethylamines. We could do this by reorganizing as I suggested above, then indicating on the list which compounds would also be considered substituted amphetamines or substituted 3,4-methylenedioxyphenethylamines.
I just don't understand the categorization at all. Why not have a listing for substituted methanes? Right, because that would be senseless. How about substituted benzenes? (Hoffer's book The Hallucinogens mentions that isoquinolines are PEA derivatives) so why not substituted 1,2,3,4-tetrahydroisoquinolines? Substituted morphinans? The number of lists we could come up with is potentially infinite - just as large as the number of compounds known.
"A large group of alkaloids are derived from phenethylamines. They include isoquinolines, benzylisoquinolines, protoberberines, aporphins, protopines, narcotine, aconitum the highly toxic delphinium poisons." (Hoffer, p.74) (the protopines would also be substituted amphetamines as well as substituted 3,4-methylenedioxyphenethylamines, narcotine, aka noscapine, would also be a substituted PEA, substituted amphetamine and substituted 3,4-methylenedioxyphenethylamine)
We should try reorganizing based on: (1) the smallest moiety of significance (in the case of PEAs, amphetamines and 3,4-methylenedioxyPEAs, it will be PEAs as it includes the latter 2 and it is ubiquitous in nature) (2) something other than the mere ability to add substituent groups onto the moiety (I mean really, you can add substituents onto any chemical) (3) an unambiguous classification (i.e. something that can be verified through a primary source, such as binding affinity for certain neuroreceptors or pharmacological activity). As I've pointed out, there is no unambiguous definition of "substituted PEA."
Bird et al. (1976) is just an example, I also know of papers discussing how opioids contain the PEA moiety, how LSD contains the PEA moiety, how N-phenethyl-2-phenylacetamide, N-phenethylbutyramide and N-phenethylisovaleramide are substituted PEAs. Why aren't those in the wiki list? My guess is because the list was mostly inspired by Shulgin's book and is arbitrarily being maintained as a list of psychoactive PEA derivatives (as evidence of this, take a look at the articles first paragraph where it's mentioned that many of them are psychoactive drugs - the same goes for the pages on substituted amphetamines and substituted methylenedioxyPEAs).
Bird PH, Bruderlein FT, Humber LG. (1976) Crystallographic studies on neuroleptics of the benzocycloheptapyridoisoquinoline series. The crystal structure of butaclamol hydrobromide and the absolute configuration and crystal structure of dexclainol hydrobromide. Can J Chem. 54: 2715 - 2722.
Hoffer A. The Hallucinogens. New York: Academic Press, 1967.
The article is clearly listcruft. Primarily relates to PEA derivatives as hallucinogens or other drugs but without any verifiable definition. Wikipedia is not a dictionary but articles should begin with a good definition - no good definition given of "substituted PEA" (relevant to: WP:OC#TRIVIA). As "substituted PEA" stands now it is WP:OC#ARBITRARY. "substituted phenethylamines", "substituted amphetamines" and "substituted methylenedioxyphenethylamines" are examples of WP:OC#OVERLAPPING. The "substituted PEA" article does not meet WP:NRVE.AlkaloidMan (talk) 09:48, 27 October 2010 (UTC)AlkaloidMan[reply]


Too long, didn't read. Is it that hard? I suggest eliminating substituted amphetamines and substituted methylenedioxyphenethylamines, due to absurd amount of overlap with this group. Reorganize "substituted phenethyalmines" into categories that are VERIFIABLE, such as "substituted phenethylamines with serotonergic activity" and "substituted phenethylamines with adrenergic activity." From a pharmacologic point of view, substituted phenethylamines includes an enormous range of compounds and the arbitrary nature of the list does not reflect that. As of now, I still see no rationale for keeping the list limited to the compounds that are listed on it (this is the who point of my argument, why not include isoquinolines, benzylisoquinolines, beznomorphans, protoberberines, aporphins, protopines and morphinans? Sure the substructure is notable from a pharmacological standpoint, but the article is only about "substituted PEAs" which can easily explode into an infinitely huge list that will overlape w/ "susbtituted amphetamines" and "substituted methylenedioxyphenethylamines." I'm agreeing with keep, but I think it really needs to be organized into sensible, VERIFIABLE categories and the subcategory lists ("substituted amphetamines" and "substituted methylenedioxyphenethylamines" need to be eliminated).

BTW, I think it's pretty lame not to read my argument. I propose we mere "substituted amphetamines" and "substituted methylenedioxyphenethylamines" with the current group and reorganize into pharmacologically verifiable groups, as opposed to this wholly arbitrary category that by all means could include the far more complex compounds I just listed.AlkaloidMan (talk) 12:09, 28 October 2010 (UTC)AlkaloidMan[reply]

"Is it that hard?" – No, but I when I read it I was tired and a bit grouchy ;-) But more seriously, your arguments would be much more persuasive if made concisely. Boghog (talk) 16:10, 29 October 2010 (UTC)[reply]
I zoned out too, and I am a pharma chemist. Reminds me of someone in college taking a phenethylamine stimulant, and talking on and on all night while I am trying to study or read. I even avoid the methylxanthine stimulants, a cup of coffee keeps me awake all night. I understand the chemical argument that there are potentially a huge number of these compounds, but only a few dozen have articles. Yes there is overlap with substituted amphetamines and substituted methylenedioxyphenethylamines, but this is just a navigation device. I think he is arguing for a name change, but that can be handled on the talk page. --Richard Arthur Norton (1958- ) (talk) 03:16, 29 October 2010 (UTC)[reply]
Keep this list is neither unlimited or unverifiable, however I agree there is a great deal of redundency with substituted amphetamines and substituted methylenedioxyphenethylamines (not to mention substituted cathinone). With the substituted amphetamines and substituted cathinones I can't see that there is much dispute they are notable, as these groups have broadly similar pharmacology and are specifically defined in law as controlled drugs in various countries. With the substituted phenethylamines it is a bit more vague seeing as this group includes many adrenergic receptor ligands like isoprenaline as well as what might be thought more "classic" substituted phenethylamines like 2C-B.
It does seem a bit superfluous to argue that things like dextrorphan or LSD could be considered substituted phenethylamines when this is just a partial element of a much larger structure, bound into multiple additional ring systems. I'd argue the same really applies to drugs like verapamil where the phenethylamine portion is really more of a side chain than the base structure being substituted on to. Whether things like sibutramine and venlafaxine would count, where they do have a substituted phenethylamine base structure but some substituents constitute additional rings, would be a bit more borderline.
Overall I would argue clean up and keep, but restrict the list to compounds that fit an agreed consensus definition of "substituted phenethylamines" - as the nominator notes there are actually many different definitions for "substituted phenethylamine" given in the scientific and patent literature, and Wikipedia guidelines call only for mentions in authoritative reliable sources, not an "official" definition. So this debate should really be about which literature definition(s) of "substituted phenethylamine" can be considered the more reliable and authoritative sources from which to derive a definition we can agree on by consensus, and the list should then be pruned to encompass only compounds that fit this definition. Meodipt (talk) 00:17, 30 October 2010 (UTC)[reply]
Keep. Nominator now suggests that article be merged with substituted amphetamines and substituted methylenedioxyphenethylamines.
Thanks for the feedback everyone. Sorry about the rambling. I do tend to go on. This post is not much different in that sense.
Yes, I've changed my mind and think that renaming / moving the article would be far more appropriate.
It does seem a bit superfluous to argue that things like dextrorphan or LSD could be considered substituted phenethylamines":
I can refer you to a few research articles that mention that dextrorphan (not specifically, but opiates in general) and LSD could be considered phenethylamines. One reason that phenethylamine is a notable moiety is because it is ubiquitous in nature, though LSD and dextrorphan are poor examples of this. There was no mention whatsoever of the fact that phenethylamine is found in 2 of the 20 common amino acids and that it (and derivatives of it) serve as a biosynthetic starting point for a very diverse group of compounds.
Originally, the article obviously had an emphasis on how substituted phenethylamines related to hallucinogens, which overlooks the significance of this relatively simple structure. I think it gave the wrong impression that phenethylamine's significance was because of hallucinogens or other psychoactive drugs.
As a starting point for a synthetic chemist, what might be considered a "substituted phenethylamine" is more limited than phenethylamine as a starting in biosynthesis. Substituted phenethylamines (and here I'm using a definition that I think we'd all agree on: tyrosine and phenylalanine) are starting points in the biosynthesis of the following substances that contain an intact phenethylamine moiety: reticuline, puromycin, capsaicin, emetine, betacyanins (e.g. betalain), anhalamine, novobiocin, coumermycin A1, clorobiocin, sinalbin,galantamine, kreysigine, morphine, codeine, turbocurarine, caranine, papaverine and marcarpine. Remember, all those are synthesized from a substituted phenethylamine and still have the phenethylamine moiety intact in the final product.
You'll see that phenethylamine is a starting point for the biosynthesis of isoquinolines and alkaloids related to or derived from it. However, even lab syntheses of isoquinolines has been performed by cyclization of (acylated derivatives of) phenethylamine. Phenethylamine has been used as the synthetic starting point for a number of morphinans (see Hellerbach et al., 1966 and references therein).
In terms of whether or not the moiety is a "significant" part of a given molecule, I have seen at least a few books and articles point out that LSD contains the phenethylamine moiety or that phenethylamine is clearly embedded in the structure of opiates, as I mentioned. Tools such as Pubmed Compound list drugs such as verapamil, fendiline, nylidrine, gallopamil and [[hexoprenaline] as being within the phenethylamine classification.
"I'd argue the same really applies to drugs like verapamil where the phenethylamine portion is really more of a side chain than the base structure being substituted on to."
That's also what formed the basis of my objection to the list. Whether or not you consider something a "substituted phenethylamine" seems to be quite subjective and in the eye of the beholder. Meodipt asserts that the list is neither unlimited nor unverifiable, so I must ask that he back up these claims. Both can be addressed by answering the following question:
(1) What is the definition of a "substituted phenethylamine?" (The answer should be verifiable. I have never seen a formal definition. IMO, since basically anything containing the phenethylamine moiety could be considered a "substituted phenethylamine," the list is potentially unlimited.)
"as the nominator notes there are actually many different definitions for "substituted phenethylamine" given in the scientific and patent literature"
I don't think these are really even definitions, with the exception of the patent literature where it is necessary for the purpose of discussion within the patent. When it comes to scientific literature, however, I have only ever seen the term used loosely, to indicate a number of possibilities. Generally, I have seen "substituted phenethylamine" (or "phenethylamine") used in research articles or scientific textbooks to refer to something that (a) a chemist could synthesize using phenethylamine (or even a substituted phenethylamine - which brings us to the world of circular logic) as a sensible starting point - the best examples of this are Shulgin's PIHKAL; (b) has phenethylamine (or a substituted phenethylamine) as a starting point in a biosynthetic pathway (not including peptides, obviously); (c) any drug where the phenethylamine moiety may have some significance in its pharmacological action (and I have seen research articles including LSD in this category, because it can be seen as a rigid phenethylamine analogue).
"So this debate should really be about which literature definition(s) of "substituted phenethylamine" can be considered the more reliable and authoritative sources"
Agreed, but I seriously doubt that you will actually find a definition other than in patents. In patents, the definition applies to what's being discussed in the patent. In other works, the only definition of "phenethylamines" I recall seeing is in PIHKAL which, if I recall correctly, simply says something about "appropriate substituents." I think that coming up with a definition will require inferring a definition from various sources based on how the term is used (perhaps this will even be considered original research). Based on how widely I've seen the term used, largely depending on the context of the discussion, I suspect we will only be able to agree on general principles of what should or should not be included on the list. We should try to derive these principles from examples in the literature (e.g. I've never seen a peptide with phenylalanine or tyrosine called a "phenethylamine" - that is clearly ridiculous, IMO, but I have seen many alkaloids referred to as either "phenethylamines" or "phenethylamine derivatives"). Given the ubiquity of the moiety, I think we should strive for an inclusive list, but simply break the list down into sub-lists with other notable substructures (for example, have links to lists of other categories that fall under "substituted phenethylamines").
I realize that was long and rambling, but I think I covered what I wanted to say. BTW, I am taking modafinil, so maybe that's why I write so much about one topic. I find that it can keep me glued to one task.
Hellerbach J, Schnider O, Besendorf H, Pellmont B. Morphinans. In Synthetic Analgesics. Pergamon Press: New York, 1966.AlkaloidMan (talk) 00:51, 31 October 2010 (UTC)AlkaloidMan[reply]
Comment I'd argue that substituted phenethylamines should fit the structure shown in the article, i.e. phenethylamine substituted with any number of substituents but not including compounds where these positions are bound together into multiple additional rings.
Obviously this would include the substituted amphetamines and methylenedioxyphenethylamines and looking at the comments above I think there may be a weak consensus forming for a merge with these. However already I'm seeing potential problems, seeing as 2C-G-5 and bromodragonfly (and I suppose even MDMA for that matter) have adjacent substitution points bridged by ring structures...but just because a substituted phenethylamine is used as a starting point for biosynthesis should not be deemed to make the final product a substituted phenethylamine, otherwise the class is as you say implausibly vast, so a line needs to be drawn somewhere.
I think common sense needs to prevail somewhat, and if the patent literature has more tightly defined and unambiguous definitions then why not go with those. Besides this, the empathogens and hallucinogens covered in PIHKAL are almost certainly what the general public would think of as "substituted phenethylamines" so it is not entirely inappropriate for the page to emphasise these particularly, though of course it must be made clear that the class includes many other assorted compounds with diverse pharmacology. Indeed it would be quite appropriate to have in the introduction to the page something about how the class is not easily defined in strict terms and that compounds like morphine and LSD contain the phenethylamine skeleton within them - but I would argue that this does not in itself make them "substituted phenethylamines". Meodipt (talk) 14:01, 31 October 2010 (UTC)[reply]
The above discussion is preserved as an archive of the debate. Please do not modify it. Subsequent comments should be made on the appropriate discussion page (such as the article's talk page or in a deletion review). No further edits should be made to this page.
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