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Add table of potency of marketed amphetamines / "substituted amphetamine" term

There seems to be confusion about the comparative potency of marketed amphetamines. I seek comments on the following table that I created. I would add citations to the molecular weights (though they seem self evident from the formulas). The remainder is simple arithmetic and needs no citations. Do the formulas need citations?

I believe this table fits here and on the dextroamphetamine page. Forgive me if the addition is inappropriate to an FA class article.

Amphetamine base in marketed amphetamine medications

drug / drug component		formula	molecular weight		amphetamine base			amphetamine base equivalence
			(g/mol)		(percent)			(30 mg dose)
			total	base	total	dextro-	levo-	dextro-	levo-
dextroamphetamine sulfate (Dexedrine®)		(C9H13N)2•H2SO4	368.49	270.41	73.4%	73.4%	—	22.0 mg	—
mixed amphetamine salts (Adderall®)					62.6%	47.5%	15.1%	14.2 mg	4.5 mg
25%	dextroamphetamine sulfate	(C9H13N)2•H2SO4	368.49	270.41	73.4%	73.4%	—
25%	amphetamine sulfate	(C9H13N)2•H2SO4	368.49	270.41	73.4%	36.7%	36.7%
25%	dextroamphetamine saccharate	(C9H13N)2•C6H10O8	450.55	270.41	56.3%	56.3%	—
25%	amphetamine aspartate monohydrate	(C9H13N)•C4H7NO4•H2O	286.32	135.21	47.2%	23.6%	23.6%
lisdexamfetamine dimesylate (Vyvanse®)		C15H25N3O•(CH4O3S)2	455.49	135.21	29.7%	29.7%	—	8.9 mg	—
Mixed amphetamine salts base percentage = sum of component values / 4.

Approximate equivalency: 30 mg dextroamphetamine ≈ 35 mg Adderall* ≈ 75 mg lisdexamfetamine (Vyvanse).

* assuming levoamphetamine and dextroamphetamine are equipotent.

Box73 (talk) 02:37, 18 August 2015 (UTC)

References

May be worth combining the tables, but otherwise the info looks good. Thanks. Seppi333 (Insert 2¢) 04:29, 20 August 2015 (UTC)

Box73, the table above is ok. The text beneath it is not. The use of the pronoun "I" is not encyclopedic and shouldn't be in a note. This also shouldn't be transcluded in, as there's no reason for a template to exist solely to transclude a table to 2 articles. I've substituted the table with the MOS fixes; please do not re-add that content. Seppi333 (Insert 2¢) 12:46, 30 August 2015 (UTC)

Small world Seppi. Hey thanks for your insightful comments. I find the one about the personal pronoun OK and have revised it. Regarding the template, I am not clear on the minimum number of pages required for a transcluded template. Could you offer a link? My sense is that even 2 articles are reasonable.

I reverted your modifications before reading your warning. My read of MOS is different than yours and let's discuss the matter here before making further changes.

I think you're reading too much into the MOS. You were OK with presenting relative potency. I'm using equivalent doses to represent relative potency because it is easier to understand. I'm not offering advice, instruction or "how to"s. Potency is relevant to such articles. Look at the opioid comparison table at opioid or better yet the morphine centric table at equianalgesic. You are of course familiar with the benzodiazepines page, since you've weeded out all references to dosing there, but the remaining table gives onset and half life just like you would find in the Merck Manual and other medical references and textbooks. Seems to me the MOS says, "Wikipedia is not a ... textbook".

There's another way. Loosen up a bit. Remember MOS also says: "Use common sense in applying it" and "If a rule prevents you from improving or maintaining Wikipedia, ignore it." WP:IAR There's a forest hidden amongst all these trees.

I'm considering the substituted amphetamines issue and will respond to that soon.Box73 (talk) 16:14, 30 August 2015 (UTC)

A unitless relative potency comparison is fine and this is made in this article when comparing the CNS/peripheral effects of the enantiomers; adding the mass makes it dosing information. The list of benzodiazepines deletions occurred as a result of 2 dialogues at WT:MED (now archived) and WT:PHARM. As a side issue, the potency of the two enantiomers differ by up to a factor of 4; they're not equivalent. Seppi333 (Insert 2¢) 16:59, 30 August 2015 (UTC)

So what? It isn't offering advice, instruction or "how to"s. Look it, I'm not listing FDA approved doses, doses recommended by Joseph Biederman, controversy over absolute vs symptom based vs weight based dosing, issues of underdosing adults, issues of asymmetrical dosing, comparing recommended doses in ADHD vs narcolepsy vs weight reduction vs off label. I could simply show the percentage of base in each marketed formulation but this is a little abstract for the average reader. Translating this into equivalent doses makes the relative potency tangible without getting into actual dosing instruction or guidelines. WP:IAR How is this not improving the articles?

You may be both right and wrong about the potency of the enantiomers. In some types of ADHD, levoamphetamine is reported to be as effacious as dextroamphetamine. Further there is evidence that the levoamphetamine in Adderall improves the effects of the dextroamphetamine portion. This is beyond the obvious. Finally, practice guidelines tend to equate dextroamphetamine and Adderall. Being the fraction of levoamphetamine is ~25% I opted to show it as equipotent and note this. Would you suggest a better factor to use? Better wording of the note?

I want to compliment you on the graphics you created of the axon terminals.

I am open to discussing changes such as rationale for substs and MOS issues.Box73 (talk) 00:14, 31 August 2015 (UTC)

I'm not going to discuss this any longer. I told you that your recent edits are providing dosing info, pointed you to a guideline, and pointed you to an identical precedent for providing data on this (i.e., the WT:MED thread and WT:PHARM thread mentioned above). That entire column is uncited and the Adderall entry is based on your incorrect assumption - the latter point is WP:Original research. I've asked for a wider input here in this thread at WT:MED. Also, IAR isn't a policy you use to re-add content (special:diff/678603025/678686571) during a content dispute. Seppi333 (Insert 2¢) 03:46, 31 August 2015 (UTC)

as Seppi333 has indicated dosing information (of any kind)should not be provided--Ozzie10aaaa (talk) 10:06, 31 August 2015 (UTC)

Ozz, funny thing is that when you came here to support the views of Seppi, he was changing the Wikipedia Policy permitting an exception for such dosing information. Thank you Seppi.

Seppi: To avoid edit warring, I will attempt discussion. Its completely up to you whether you choose to participate in a discussion on a talk page.

Please notice the equipotent doses column you say is unsupported is simply the scaled reciprocal of the "percent base" column you find acceptable. It isn't original research because it comes from routine calculations:

base molecular weight / total molecular weight = % base (potency)

total molecular weight / base molecular weight = 1 / % base = equipotent dose (no specific unit) ←this amount can be scaled and any mass unit attached.

See the revised Amphetamine base in marketed amphetamine medications page/notes.

It is too simplistic to call the "Adderall assumption" used in the table incorrect. Depending on the effect, levo is less potent, similar or even more potent compared to dextro. In simplest terms dextro has more central effect and levo more peripheral effect. In subtypes of ADHD levo is as effective as dextro. Hence you have seen Adderall far surpass Dexedrine in clinical use, and now the entry of Evekeo. But I concur: dextro is 4x levo in re central stimulant effects. But potency depends on what is being measured.

Also consider FDA and other guidelines. FDA dosing for dextroamphetamine s., Adderall and amphetamine s. are identical. ADHD authorities (Joseph Biederman & associates for one) use identical dosing ranges for dextroamphetamine and Adderall. Given all of this variance, I had made a reasonable assumption in the table and clearly noted that assumption. Because of the amount of levo in Adderall and the identical dosing, I didn't believe this would be a significant issue. I reconsidered this and believe you are right; it is appropriate use the 4x value but also include the equal value. I am swayed also because of the entry of Evekeo (amphetamine sulfate, now added).

Now these could be left in a unitless factor. Scaling them to a realistic mg value makes it more comprehensible for a general audience.

I have revised the original template table as you might see. I invite your comments.

It is obvious you are very deeply invested in this article and related articles. Let us try and find reasonable compromise. In the benzodiazepine talk threads maybe I missed something but I didn't see much discussion or attempt to try and find support for the contribution; simply the surgical option.

Re contraindications, it is frustrating to see items listed simply based on package inserts ignoring accumulated evidence to the contrary or demoting it to footnotes. Now I'm not comparing this to the fear mongering of the antipsychiaty folks that has sometimes invaded Wikipedia. (When Peter Breggin condemns ECT for depression and antiseizure meds as mood stabilizers for mania, what would he do for epileptics?)

Re substituted amphetamines, I think it is a valid term technically. However it has three major issues:

1. Outside of Wikipedia "substituted amphetamines" is infrequently used in reference to amphetamine itself. "The amphetamines" or "amphetamine type stimulants" is more commonly used.

2. When used, it usually refers to derivatives, such as methamphetamine and especially MDMA etc.

3. Using "substituted" technically expands the drug class far beyond what are conventionally considered the amphetamines.

So where amphetamines causes confusion with amphetamine itself, substituted amphetamines causes confusion with everything but amphetamine itself—amphetamine derivatives. (If substituted amphetamines is the best name then we should also say substituted benzodiazepines or substituted barbiturates to name a few?)

Consider a student researching a paper on amphetamines starting at Wikipedia and learning the class is called "substituted amphetamines". So he then researches "substituted amphetamines" and generally finds material about MDMA type drugs and methamphetamine, finds little about amphetamine itself and misses many of the most appropriate mainline reviews using the conventional term amphetamines.

I am seeking clarification about Wikipedia naming policies re ambiguity and common names specific to this dilemma. I fear some may have fallen in love with the term "substituted amphetamines".

The solution to "amphetamines" vs "substituted amphetamines" I propose is "the", that is, call the drug class "the amphetamines".WP:NCMED/WP:NAME Substituted amphetamines creates the very problem it solves, but in the outside world, outside the reach of Wikipedia editors but close at hand for Wikipedia users. Box73 (talk) 13:34, 6 September 2015 (UTC)

• Your recent revision to the dosage comparison column looks fine; there's no potential MOS/policy issues of which I'm aware and it's now consistent with referenced statements in the article.

This is the structure of phenethylamine with its substitution points marked.
Substituted phenethylamines are formed by replacing the hydrogen atom at these points with substituents.

E.g., substitutions at these points that involve a methyl group as the substituent yields the methylphenethylamine isomers.

• As for the terms "substituted amphetamines", "amphetamines", and "amphetamine-type stimulants", there's a few things that need to be said about the definition of these classes, which are not identical classifications. I'll elaborate on this when I have more time, but in a nutshell, "amphetamines" is by far the most common term basically just because it is the only MeSH term for amphetamine-related compounds. MeSH terms are pubmed-indexing terms for papers that cover particular topics, so the journal articles that include a list of MeSH terms and cover amphetamine, its analogs, or its derivatives will probably be indexed with "amphetamines", which makes it searchable under that term as well. MeSH terms also are associated with particular definitions to clarify indexing terms. The "amphetamines" MeSH definition (all derivatives, all analogs) happens to be an enormous set of compounds which is far larger than the "substituted amphetamine" class (a specific subset of amph derivatives).
• "Amphetamine-type stimulants" does not appear to have a standardized chemistry (functional/structural) definition (the UNODC usage represents a legal classification of banned stimulants - page 5 - some aren't substituted amphetamines). Like "substituted amphetamines", it isn't a MeSH term; unlike "substituted amphetamines", the name itself does not indicate specific inclusion criteria for identifying compounds that belong in the class (i.e., there's no indication of what attribute of a compound makes it an "amphetamine-type" chemical).
  
  There's obviously a fair bit of overlap between "amphetamines" and "substituted amphetamines", but these terms both have a standardized definition which are not identical: every one of the "substituted amphetamines" (the class of amphetamine derivatives that are formed through substitution reactions involving the amphetamine compound and various substituents - in simplest terms, substituted amphetamines are compounds that contain the amphetamine compound somewhere in their structure drawings) is a member of the "amphetamines" class (a class of all amphetamine derivatives and analogs), but the reverse is not true. Seppi333 (Insert 2¢) 17:30, 6 September 2015 (UTC)

Edit: the above blob of text is the short version; I'll elaborate more on this when I have time. Seppi333 (Insert 2¢) 18:15, 6 September 2015 (UTC)

• I've added the structure-based definition of this class to the article under the derivatives section. Seppi333 (Insert 2¢) 02:05, 11 September 2015 (UTC)

• Regarding contraindication, I don't put much stock into any contraindication information. Contraindications are basically cautionary statements based upon drug interactions that are intended for doctors/patients merely as guidance. Do I think all of the contraindications in this article reflect an actual drug interaction to avoid? No. I don't think there's clinically relevant interactions associated with a few of the listed contraindications, but I added them anyway to satisfy the featured article comprehensiveness criteria. The underlying interactions are sometimes based upon data from models of pharmacodynamics interactions instead of clinical data, hence the potential for error. In contrast to Contraindications, the Interactions section focuses mostly on established clinical interactions (most of which are pharmacokinetic interactions) and has cursory coverage of model-based interactions of amphetamine with various drug classes. Seppi333 (Insert 2¢) 18:15, 6 September 2015 (UTC)

WikiProject Chemicals quality rating

Why does the banner for the Chemicals WikiProject show this article as A-class when it is FA-class? The parameter is FA in the template. Sizeofint (talk) 03:21, 18 August 2015 (UTC)

WP:CHEMS doesn't use FA ratings - don't know why. Other FA chem articles have the same rating; e.g., see Talk:Acetic acid. Seppi333 (Insert 2¢) 04:30, 20 August 2015 (UTC)

Drugbox

@Sizeofint: I noticed the INN name + link you added to the infobox a few days ago. It may be worth requesting an INN field be added to the drugbox as a parameter if you think it's worth clarifying these; at present, it actually violates the MOS to place this in the title with a link: Wikipedia:Manual of Style/Infoboxes – The template should have a large, bold title line. Either a table caption or a header can be used for this. It should be named the common name of the article's subject but may contain the full (official) name; this does not need to match the article's Wikipedia title, but falling back to use that (with the {{PAGENAME}} magic word) is usually fine. It should not contain a link. Seppi333 (Insert 2¢) 00:39, 11 September 2015 (UTC)

I saw this diff on morphine and assumed we had a consensus going about this. If there isn't, this is something that needs to be discussed. Sizeofint (talk) 06:34, 11 September 2015 (UTC)

I personally don't really care one way or another about the title - I'm indifferent to changing the MOS guideline vs changing the article; however, the article needs to reflect the guideline because it's a featured article (criteria #2). Regarding the lack of objection, I'm assuming the guideline entry just hasn't been pointed out until now. Seppi333 (Insert 2¢) 07:05, 11 September 2015 (UTC)

Ty for compromising. I've added an alternative to linking the INN in the title; the MOS doesn't prohibit the use of {{abbr}} on a term. Seppi333 (Insert 2¢) 14:31, 11 September 2015 (UTC)

That's a good idea. I'll probably use that on the other infoboxes. Sizeofint (talk) 14:49, 11 September 2015 (UTC)

Subst. amph. definition

@Boghog: Can you check over and revise my recent addition to the Amphetamine#Derivatives section: "specifically, this chemical class includes compounds that are formed by replacing one or more hydrogen atoms along the core amphetamine structure with substituents"? Thanks, Seppi333 (Insert 2¢) 01:47, 11 September 2015 (UTC)

Looks good. I made a minor tweak. Boghog (talk) 05:17, 11 September 2015 (UTC)

Thanks again, I appreciate it. Seppi333 (Insert 2¢) 05:38, 11 September 2015 (UTC)

Effects on reaction time

In the "Enhancing performance" section, one sentence says amphetamine reduces reaction time. The next sentence then states it improves reaction time. Is one of these incorrect or is the literature really split on this? Sizeofint (talk) 05:11, 21 October 2015 (UTC)

Improving reaction time is reducing reaction time: lower is better. Seppi333 (Insert 2¢) 06:13, 23 October 2015 (UTC)

Ah, makes sense. Don't know what I was thinking. Sizeofint (talk) 07:35, 23 October 2015 (UTC)

Enhancing performance section

The first sentences in the enhancing performance section is "In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults;..." but I think it misrepresents what the studies say. The first is (as far as I can tell), not about healthy humans; the second is much more cautious in its conclusion than this sentences. I propose to change the sentence to the following: "In 2015, a systematic review and a meta-analysis of clinical trials found that, when used at low (therapeutic) doses, amphetamine probably produces modest improvements in cognition in normal healthy adults;..."--Snipergang (talk) 12:23, 6 November 2015 (UTC)

Neither paper uses uncertain language when discussing the statistical significance of an effect on specific components of cognition; however, the second paper suggests that the aggregate effect is uncertain but likely modest. For brevity and simplicity, the sentence omits a description of effect sizes, since the descriptions of the effect size associated with different aspects of cognition varied by aspect and between the 2 reviews. At present, that sentence just says "an effect exists" instead of describing how much of an effect exists for each component of cognition like the 2nd review's abstract did (medium size for delayed episodic memory; small size for short-term episodic memory, working memory, inhibitory control). It seems fine to mention that the aggregate effect size is modest overall, so I added that in. Both reviews cover healthy adults as well as individuals with ADHD - they're linked below.

• 1st review
• 2nd review

Seppi333 (Insert 2¢) 15:51, 6 November 2015 (UTC)

Thank you for highlighting the difference between individual and aggregate effect and for the links. I only had the abstracts to work with. --Snipergang (talk) 08:25, 8 November 2015 (UTC)

Drug box issues, medical, substituted amphetamines and substituted templates.

Routes of administration: Since Benzedrine inhalers are long gone, nasal inhalation should be eliminated from Medical, or somehow qualified.

• The data in the dbox is based upon refs that suggest it is still used as a decongestant. The pharmaceuticals are based almost entirely on American formulations. I'm not sure if there are no inhalers available in any country, but based upon the refs which suggest its use as a decongestant, there probably are inhaler formulations in some countries. Seppi333 (Insert 2¢)

Metabolism. I'm confused between "amphetamine only" and "other". Does "other" mean active metabolites?

• Yes, although "Other", which referred to any of its metabolites, was removed a while back. "Amphetamine only" refers to enzymes which metabolize amphetamine itself. Seppi333 (Insert 2¢)

Onset of action: This gets into medical vs recreational distinctions as well as site of action (central vs nasal). 

1. We should to divide IR into oral and intranasal/intravenous. Perhaps IR (oral) and IR (intranasal/intravenous). However since XR refers to oral, and IR tends to be used for oral, keep XR and IR for oral, and isolate intranasal/intravenous. Perhaps IR, XR, IN/IV?
2. Despite IR standing for immediate release, oral IR effects certainly are not immediate. Immediate only means it isn't a time release / sustained release / extended release formulation. The time to be ingested, absorbed, cross the BBB, accumulate concentrations to cause clinical effect exist.
3. IR and XR (oral) should both have the same onset since a part of the (larger) XR dose is in IR form.
4. The reported value for IR oral is 30-60 minutes. (I don't have the references at hand, but they vary by source.)
5. Although IN or IV is almost immediate, I suggest "rapid" over "immediate". (Also relieves confusion with immediate release.)

• Buccal/sublingual administration can introduce a fraction of a dose of amphetamine into the brain (and other organs) almost immediately upon partially dissolving. I'm fine with giving a range here if you think it's helpful, but in truth, a lower limit to the amount of time that it reaches various body tissues really just depends on how rapidly the pill dissolves and is subsequently pumped through the blood stream. For now, I've changed IR from "immediate" to "rapid" as you noted above, unless you'd prefer using a range here. Seppi333 (Insert 2¢)

I should have been more clear. My main issue is distinguishing pharmaceutical IR (taken as intended) from recreational forms/use. (Not taking this precaution leads readers to false concerns and conclusions and will be exploited by those engaging in fear mongering.) These values would come from drug monographs and medical references just as occur for XR.

You're probably right about the buccal/sublingual and I believe this also is true of nasal administration. But the issue gets muddy. If one is doing this with IR tablets there is considerable filler slowing the process, perhaps delaying the threshold of effect. This is further complicated by tolerance and tachyphylaxis, and exactly what effect is measured. But as noted, my concern was listing pharmaceutical IR values.— Box73 (talk)

I'll add a range for oral IR dosing in the next day or two. Seppi333 (Insert 2¢) 21:11, 9 December 2015 (UTC)

The refs used so far simply describe an IR onset as "fast". There's no time range given. I don't think it's really necessary to go beyond a descriptive term in this case; if you find a ref for the onset of IR formulations, we can add it. Seppi333 (Insert 2¢) 19:31, 11 December 2015 (UTC)

Duration of action presents the same issues as onset. I believe the current IR values listed are for oral amphetamine, either Adderall or pure racemic forms. (That is another reason the onset value for IR should be oral.) I am skeptical that these values are for non oral administration (and decongestant effect) which might have different durations and possibly slightly different half-lives (for example, the decongestant is local vs systemic).

• The durations of action are based upon their use for ADHD and narcolepsy. They probably vary like plasma half-life; I haven't come across an extended range in citations though. Seppi333 (Insert 2¢)

Medical. "Amphetamine ... is sometimes prescribed for its past medical indications ... such as ... nasal congestion."

Cut nasal congestion. Amphetamine is no longer prescribed as a decongestant. Currently, psychiatrists do sometimes prescribe amphetamine for depression and rheumatologists occasionally for chronic fatigue syndrome. However, the Benzedrine inhalers are long gone and no competent provider would prescribe oral amphetamine (or d-amphetamine) for congestion.

As mentioned, chronic fatigue syndrome might be a potential candidate for notable off-label use. I'm collecting sources and will follow up.

• There's more than one current medical refs which assert its use as a nasal decongestant. E.g., the ref citing the rhinitis medicamentosa side effect (this is quoted in the reference). There are probably a range of off-label uses which aren't currently mentioned in the article. If you come across citations which mention others, feel free to add/cite them; it may be easier to just note them here though since the source code of the first medical uses paragraph is somewhat complicated due to {{if pagename}} templates. Seppi333 (Insert 2¢)

I'm skeptical. Ramey et al's article about rhinitis medicamentosause uses "decongestant" to mean agents with a decongestant effect, not agents used clinically to relieve congestion. Look at the list—do you know of any doctors prescribing mescaline for congestion?

Amphetamine's reputation and abuse potential have eliminated this use. I can find no evidence for current clinical use as a decongestant. — Box73 (talk)

Fair enough - removed. Seppi333 (Insert 2¢) 21:11, 9 December 2015 (UTC)

Amphetamine derivatives. The definition of Amphetamine derivatives is right on. As my friend Seppi would guess, my two issues deal with substituted amphetamines: (note: I recognize that this issue is wider than the amphetamine article itself and certainly belongs to the substituted amphetamines article.)

• It is equating "amphetamines" with "substituted amphetamines".
• It is saying both are common terms.
• It (referring to substituted amphetamines here as derivatives) is meant to recognize/satisfy criticisms (I've raised) while continuing to use it inclusively elsewhere.

"Amphetamines" is a common term and commonly includes amphetamine (and its enantiomers) as well as derivatives. (The extent of the derivatives varies.) "Substituted amphetamines" is not a common term but a somewhat esoteric term and frequently excludes amphetamine and its enantiomers. Its esoteric nature makes it difficult to collect many definitions. (If we search Lithuanian literature, we would find Lithuanian terms to be common, but outside of Lithuanian literature, the Lithuanian terms would be rare. They are esoteric. Should we use Lithuanian literature to demonstrate that the terms are common (i.e., popular) generally? (except in Lithuania.)

At the risk of beating a dead horse, here are my overdue sources dealing with substituted amphetamines:

Amphetamine is clearly excluded in these quotes from different versions of a classic psychiatry reference:

The classic substituted amphetamines include MDMA, MDEA, 2,5-dimethoxy-4-methylamphetamine (DOM, STP), dimethyltryptamine (DMT), MMDA, and trimethoxyamphetamine (TMA), which are also commonly classified with amphetamines. — Kaplan and Sadock's Pocket Handbook of Clinical Psychiatry

With a few notable exceptions, animals in experimental situations self-administer most of the drugs that humans tend to use and abuse. Included among the drugs are μ- and δ-opioid agonists, cocaine, amphetamine and amphetamine-like agents, substituted amphetamines, such as MDMA, alcohol, barbiturates, many benzodiazepines, a number of volatile gases and vapors (e.g., nitrous oxide and ether), PCP, and nicotine. — Kaplan & Sadock's Comprehensive Textbook of Psychiatry

In the first quote above note that he said, "also commonly classified with amphetamines" not "also commonly classified as amphetamines"   This literally distinguishes amphetamine from substituted amphetamines:  

Amphetamine and substituted amphetamines, including methamphetamine, methylphenidate (Ritalin), methylenedioxymethamphetamine (ecstasy), and the herbs khat and ephedra, encompass the only widely administered class of drugs that predominantly release neurotransmitter, in this case principally catecholamines, by a non-exocytic mechanism. — "Mechanisms of neurotransmitter release by amphetamines: a review" in Progress in Neurobiology

The following text likewise excludes amphetamine from substituted amphetamines. In fact it would exclude not only amphetamine but close congeners such as ephedrine and methamphetamine; this may explain the distinction between "amphetamine-like agents" (or "amphetamine-type stimulants") and "substituted amphetamines" (or Ecstasy) as used in Kaplan.

MDMA is one of a number of closely related substances known as substituted amphetamines.... The substituted amphetamines are entirely synthetic ... in most western countries substituted amphetamines are illegal... Some ecstasy tablets many not contain any substituted amphetamines at all, they may contain methamphetamnine, LSD, ketamine or inert substances. — Drink, Drugs and Dependence: From Science to Clinical Practice

These chapter end questions is Fundamentals of Pharmacology allude to the distinction of amphetamines from MDMA, which is commonly referred to a substituted amphetamine.

3. What is the chemical name for ecstasy? To which class of drugs is it closely related? ... 5 Compare and contrast the effects of ecstasy with those of amphetamines. — Fundamentals of Pharmacology

A Penn State Dept. of Chemistry PowerPoint presentation includes a slide graphic showing amphetamine as the source but excluding it from the class. Note yellow color of title and substituted amphetamines structural diagrams vs red for amphetamine.

Substituted amphetamines is a technical term used by chemists. Similarly substituted morphinans or simply morphinans is a technical term used by chemists which includes morphine and its many congeners. Neither are commonly used. We don't talk about the abuse of prescription (substituted) morphinans. We don't commonly call heroin a (substituted) morphinan. We don't say morphine derivatives are commonly called opioids and (substituted) morphinans. To do so is a promotion of the esoteric term to the level of the common term. Now I can find the term morphinans used by chemists and toxicologists but not in common usage. Chemists and toxicologists use "substituted amphetamines" to include amphetamine itself and all its derivatives. But the term, while a bit more common than morphinans is not common and when applied in medicine and pharmacology is typically not inclusive or not used. By contrast, the term amphetamines is common and always includes amphetamine itself, it almost always includes chemically related stimulants, and frequently MDMA type derivatives with psychedelic properties.

The problem here is, of course that amphetamine is a chemically derived name like barbiturate and benzodiazepine, yet we don't commonly add substituted to them. Looking at other psychoactive drugs, we have the modern term opioid which spans morpinans (which includes opiates) and non-morphinans (which are unrelated structures). (The mutually exclusive meaning of opiate and opioid is passing as opioid becomes the umbrella term.) So opioid has become a functional class. So too antipsychotic, anticonvulsant (or increasingly anti seizure/epilepsy medication), mood stabilizer (which is lithium and many anticonvulsants). Then there are tranquilizer, major tranquilizer, neuroleptic and so on which are either antiquated or vernacular. These are all functional classes.

The problem here is, of course that amphetamine is a chemically derived name like barbiturate and benzodiazepine, yet we don't commonly add substituted to them. Like amphetamine (unintended pun) we have phenethylamine.(aka phenylethylamine) and cathinone. Both are a substance and a chemical drug class. The substances are not generally encountered as often as amphetamine, in use or language, and the classes occur with and without "substituted". Here again, we see chemists and Wikipedia using substituted X, but commonly just X as the drug class. When substituted X is commonly used, it is exclusive of X: derivatives of X or X with substitutions. So here too the inclusive definition is pretty much common to chemists and Wikipedia. They present the same potential mistranslations as substituted amphetamines, but fewer real linguistic dangers because they aren't commonly encountered (or much less frequently).

Consider the related term substituted cathinone. A recent article "Emerging drugs of abuse: current perspectives on substituted cathinones" begins: Substituted cathinones are synthetic analogs of cathinone... Like substituted amphetamines, substituted cathinones is generally used to refer to derivatives: in this case so called "bath salts".

In all the medical literature I searched, I never found the term "substituted amphetamine psychosis", "substituted amphetamine dependence" or "substituted amphetamine withdraw", though all of these are true for (and likely more frequent with) methamphetamine, which technically is a substituted amphetamine, and various other amphetamine derived stimulants.

• I've clarified the derivatives section. I'm assuming that was the relevant issue in the text. Seppi333 (Insert 2¢)

I appreciate that. I want to find a fair compromise as you do.— Box73 (talk)

Inclusive use of "substituted amphetamines".

I have found that toxicologists are those tending to use substituted amphetamines and using it in the inclusive sense. For example James O'Callaghan "Neurotoxic effects of substituted amphetamines in rats and mice" a chapter in Handbook of Neurotoxicology, Vol II and another book titled Neurobiological Mechanisms of Drugs of Abuse: Cocaine, Ibogaine, and Substituted Amphetamines. Although the latter is a collection of papers presented at a seminar on drug abuse, substituted amphetamines is only used two articles, one being the chapter/paper co-written by O'Callaghan and the editor. Another toxicologist is George Ricaurte, a controversial anti-drug researcher best known for a retracted article in the journal Science where methamphetamine toxicity was attributed to MDMA. My impression is that these fellows never met an amphetamine that wasn't toxic and the term "substituted amphetamines" was being used as a melting pot. O'Callaghan for example, concerned about therapeutic doses of amphetamine used in ADHD writes, "[I]t is not uncommon to see all substituted amphetamines labelled as potentially or outright neurotoxic." which he disavows but seems to arrive at anyway by discussing asymptomatic brain changes such as dopamine deficits prior to the presentation of Parkinson's. He and Miller seem rather loquacious, expansive in terms of toxicity, eager to apply rodent research to humans and fond of the term "substituted amphetamines". What I'm saying is "substituted amphetamines" is being used by those with a scientific prejudice or a political agenda, particularly Ricaurte. But all that aside, these toxicologists impress me as predominant published users of "substituted amphetamines" inclusive of amphetamine—Wikipedia and them.

The other issue is what I cannot cite. All of the books, papers and journal articles by credentialed professionals that never use the term substituted amphetamines. All of the physicians that had to take organic chemistry to get into med school who don't use substituted amphetamines or use it differently when they publish. All of the editorial boards who don't promote the term. The lack of letters to JAMA or various neuropsychiatry journals complaining about the ambiguity of the term amphetamines. The term isn't common.

• Regardless of what toxicologists or others write, the convention is to include the parent of a class of a substituted compounds in that class. This is a convention used in virtually every wikipedia page on a class of substituted compounds as well. Arguing this point further is really just beating a dead horse.

And, FWIW, bupropion and phentermine are quite clearly not neurotoxic substances, but they're both obviously substituted amphetamines. Seppi333 (Insert 2¢)

re FWIW: I imagine he'd consider phentermine to share the mechanisms and liabilities of amphetamine. Can't say about long term bupropion.

Seppi is addressing this as a technical naming convention; I am approaching it as the actual use of the terms. But my concern is specifically the preferred or primary use of "substituted amphetamines", not specifically the derivatives section.

Wikipedia cannot simply disregard other reliable sources. Amphetamine is not just another chemical or functional group. It does not serve our general audience to disregard common and medical usage to promote some systemic neologism.

I agree that "substituted" is also attached to related drugs: substituted methylenedioxyphenethylamine, substituted phenylmorpholine, substituted cathinone. These are all lesser known drugs than amphetamine/s, and without a preexisting convention.

In this case it is academic whether a parent compound belongs in the class of derivatives or not. Rather it is that the existing term "amphetamines" is widely known and used. Since no apparent ambiguity occurs from "amphetamines" (demonstrated by its use), but does for "substituted amphetamines" (as I showed), Wikipedia should primarily use amphetamines. Sometimes systemic naming conventions are unconventional to an encyclopedia's general audience. Despite my apparent equestrian battery, I am guided by three aphorisms: 1. If it ain't broke, don't fix it; 2. Don't write to impress, but to communicate; 3. The KISS principle. — Box73 (talk)

The reason I hate the generic term "amphetamines" and prefer to use "substituted amphetamines" in this article is that the former has a definition which is so vague/broad that it's difficult to accurately and precisely describe the entire set of compounds to which it refers. Even if the latter term is unknown to most people, it's still preferable to the former because it's a well-defined set instead of an ambiguous set of compounds. In any event, simply deleting the "substituted" term throughout the article would make a few of the statements in the text inaccurate; this includes all statements covering the definition and members of the class. Seppi333 (Insert 2¢) 21:11, 9 December 2015 (UTC)

Regarding the template Amphetamine base in marketed amphetamine medications, this was changed from transcluded to substituted on the grounds that two articles are not sufficient reason to transclude a template. After consultation, I can find no Wikipedia policy concerning a minimum number of articles being required for transclusion; this would not be a reason to substitute the template (given two or more articles access the template). Obviously transclusion is more efficient in improving the content. If transclusion is acceptable at Dextroamphetamine, Adderall and Lisdexamfetamine, I can see no reason why it needs to be substituted instead at Amphetamine. Concerns over content effect all articles the template is transcluded in, so transclusion, with discussion and editing at the template itself, would benefit all of these articles.

After reviewing the improvements of syntax and tweaking of references in the substituted copy, most have been incorporated into the base template, the exception being revisions to the syntax of the chemical formulas which would permit the formulas to break. Line breaks in the formulas would be confusing and visually burdensome. Likewise I maintained the heavier dot, as the standard dot is difficult to perceive with some resolutions and for some people.

The substitution raises issues of ownership (WP:OWN) as this would maintain control over a certain article rather than resolving common issues. (How do the changes to the substituted template apply only to the amphetamine article?) Given the previous reasoning and to correct appearances of ownership, the transclusion of the Amphetamine base... template should be restored and improvements shared by all. Box73 (talk) 13:38, 19 November 2015 (UTC)

• The "Amphetamine pharmaceuticals" table is used in this article and in the dextroamphetamine article. It's not transcluded as a template. The more templates that are transcluded into this page creates more of a potential for sneaky vandalism/template vandalism, which is why I'm disinclined to create lots of templates that transclude onto this page. That's really all there is to it. Seppi333 (Insert 2¢) 22:35, 22 November 2015 (UTC)

Edit: if there's consensus to add this in all of the above articles, it may be worth using a transclusion. Again though, in general, lots of transclusions=bad. As an example, the Addiction glossary template which is transcluded into this article has been vandalized several times since it was created last year (e.g., [1] [2] [3]). Unlike this article, it is not a protected page. Seppi333 (Insert 2¢) 05:42, 23 November 2015 (UTC)

It is true that transclusion permits edits, good and vandalous to occur, effecting multiple articles. Just as templates invite vandalism they also reduce wikistress. Fortunately vandalism is easy to undo. It sounds like the solution should be to request some level of protection for these templates.

It is curious that the addiction glossary template—cited for for repeated vandalism—justifies substitution of other templates but not that template itself.

The addiction glossary seems to be in need of alphabetizing. MOS:GLOSSARIES There does not seem to any rationale for the existing order. It might make sense to add tachyphylaxis to the list which relates to binge use, but this isn't central. — Box73 (talk)

If it means that much to you, we can transclude it; I'll need to fix some minor table and reference formatting issues first though. I'll try to do this within a day or 2.

In regard to glossaries, template glossaries are outside the scope of MOS:GLOSSARIES, which applies to glossary articles (e.g., Glossary of gene expression terms and other "Glossary of..." articles). For comparison with the article glossary: Template:Transcription factor glossary isn't alphabetized. Seppi333 (Insert 2¢) 21:11, 9 December 2015 (UTC)

Reflist
References

In the future, please don't write an essay of 20000 characters to raise concerns like this; many editors, including me, would rather not read that much text if the issue can be explained more concisely. Seppi333 (Insert 2¢) 22:39, 22 November 2015 (UTC)

What? 20000 characters? Did you remember to count the punctuation and blank spaces as characters? It was actually about 2200 words excluding the citations, about half properly redressing "substituted amphetamines", which I assume is the "concerns like this" allusion. I was fairly concise in the majority of the issues raised. But I'll try and take it easy.

Forgive my delay but thank you for your response to my concerns. — Box73 (talk)

I was referring to the added characters listed in the page history for that edit (+20,041). Seppi333 (Insert 2¢) 21:11, 9 December 2015 (UTC)

Regarding the deletion of benzyl methyl carbinamine

From Seppi's recent edit summary

(we don't include the majority of amphetamine synonyms ( http://www.commonchemistry.org/ChemicalDetail.aspx?ref=300-62-9 ). I've removed the term and redirected Benzyl methyl carbinamine here since it doesn't seem to be widely used or notable)

I appreciate that there is a difference of opinion.

α-methylphenethylamine is the best synonym in part because it was the source of the term amphetamine There are many other synonyms of amphetamine, more than could or should be listed, yet my addition was not capricious. Benzyl methyl carbinamine was the original synonym (name) used in the 1930s. It is notable that Alles derived "Benzedrine" by combining "BENZyl methyl carbinamine" with "ephEDRINE". For the first several years benzyl methyl carbinamine was widely used to identify the drug, typically parenthetically following Benzedrine. In fact, "amphetamine" was little used originally.

The American Chemical Society database at Common Chemistry is a reliable source but not the gatekeeper of acceptable synonyms. Benzyl methyl carbinamine is listed elsewhere. Wide usage exists in early medical literature—secondary sources concerning the name. Benzyl methyl carbinamine is not trivial. The term was used by the process inventor (Alles), manufacturer (SK&F), and notable physicians such as Bradley reporting his discovery treating attentional disorders. (β-phenylisopropylamine was another early term encountered.)

Wikipedia editors are encouraged to develop drug infoboxes and the field "synonyms" currently lists but a single term. Benzyl methyl carbinamine is historically notable and widely used, and is reasonable to include. Pending any remaining objections, the deletion should be reverted with improved citations (1 or 2). — Box73 (talk) 03:06, 13 January 2016 (UTC)

Are there any other synonyms of similar historical value? If this is the only one with significant historical value or one of only a few I think it is reasonable to include it. Sizeofint (talk) 06:22, 13 January 2016 (UTC)

Thank you Sizeofint. In chemical literature, many. But in early medical literature benzyl methyl carbinamine dominated until amphetamine. Further, there were many brand names obviously derived from the many chemical names, but the original and famed, Benzedrine, was derived from benzyl methyl carbinamine (+ ephedrine). I don't know 1930s-40s customs but benzedrine / benzedrine sulphate were sometimes used (lower case) as trivial generic names and this alludes back to benzyl methyl carbinamine. — Box73 (talk) 14:29, 13 January 2016 (UTC)

References

Ive never even heard this term before. It's not on pubchem or drugbank. The only one mentioned somewhat frequently in current articles I've read is it's original name: phenylisopropylamine. I see no reason to add yet another name to the article if it isn't even listed in our linked databases. Seppi333 (Insert 2¢) 08:32, 13 January 2016 (UTC)

Thanks Seppi. First, I think β-phenylisopropylamine would be another appropriate candidate. The fact that benzyl methyl carbinamine is neglected in chemical references but widely represented in historic medical literature is precisely why is should be included—Wikipedia is encyclopedic. As said, benzyl methyl carbinamine dominated early medical literature (as a generic term) until amphetamine was sanctioned by the AMA. We need to see this historically and medically as well as scientifically; we need be comprehensive. You have heard "Benzedrine" which was derived from benzyl methyl carbinamine (+ ephedrine).

Why are published databases without the term? My learned impression is that benzyl methyl carbinamine was scratched out mainly because AMA wanted their term "amphetamine" and source "α-methylphenethylamine" to replace it (and partly because benzedrine (lower case b) became used as a non-proprietary name). But follow my citations above and let me & Jimmy Hoffa know what you think. — Box73 (talk) 14:29, 13 January 2016 (UTC)

@Box73: Given that this seems to be the name from which Benzedrine was derived and the fact that it is not in common use in any monograph or major chemical database or in pubmed, it appears that it is significant in a historical context, but not significant as a synonym in current use. It seems appropriate to note the historical derivation, so I've added this material from the first ref here: Special:diff/700007611/700105465. I'm hoping this addresses your concerns. Seppi333 (Insert 2¢) 12:41, 16 January 2016 (UTC)

@Seppi333: You beat me to it, though it belongs here too since this is the article about Benzedrine, so to speak. The term doesn't appear in the 10th edition (1983) of the Merck Index either but there are reliable sources about amphetamine that don't list the drug's scientific properties and countless reference identifiers. I'll reverse what you said: Benzyl methyl carbinamine may not be significant in current use, but it is significant as a synonym historically. (I mean, Benzedrine isn't in current use and hasn't been for some time, but Evekeo is; which is more significant, more known?) I'm not in a rush but phenylisopropylamine and benzyl methyl carbinamine aren't inappropriate and should be added/returned. I appreciate your reasoning and passion about this article and I'm hoping you do the same towards me. — Box73 (talk) 10:43, 20 January 2016 (UTC)

"Phenylisopropylamine" is already mentioned in the article in the history section. Given that the history section is supposed to be a summary of several sections of another article, it shouldn't contain every single detail which is contained in the other article. If you want to expand on the history, edit the material in the history article - that's where people are supposed to go to find/read content on that topic. Seppi333 (Insert 2¢) 14:38, 21 January 2016 (UTC)

Disappearing infobox edits, addiction templates beyond the scope of this article, moving split history article

In a recent edit, I added the missing trade names field in the drug infobox. These included the three current trade names and the legacy trade name Benzedrine which is widely known and represented in the literature. This edit was removed without talk page discussion or even summary comment. The template field "tradenames" exists and is clearly appropriate to complete, regardless of whether the trade names appear in the article text itself. In fact, other information in the amphetamine infobox is taken from monographs of those very brand drugs. I hope we can act without practicing ownership nor precipitating edit warring. I invite that editor or others to resolve the issue with me.

The "Summary of addiction-related plasticity" template and the "addictions glossary" template belong in an article on addictions. The "Summary of addiction-related plasticity" is a large table providing a comparison of 6 different reinforcers by 13 behavioral or biological effects. While aerobic exercise in mentioned as a potential behavioral therapy, the table is superfluous to this fact and clearly beyond the scope of amphetamine. Likewise the addictions glossary, collapsed or not, defines terms not used here and is beyond the scope of amphetamine; it is also appropriate in the addictions article.

RE: the second paragraph in overdose

Individuals who frequently overdose on amphetamine during recreational use have a high risk of developing an amphetamine addiction, since repeated overdoses gradually increase the level of accumbal ΔFosB, a "molecular switch" and "master control protein" for addiction.

This should be reworded. I didn't find the cited sources to say this, rather one stated that overdose is a consequence of addiction. The issue is a duality of overdose definitions, which Merriam-Webster defines: "too great a dose (as of a therapeutic agent); also : a lethal or toxic amount (as of a drug)". The cited author is using the second definition, (as applies to abused drugs) and for that very reason this editor shouldn't cite him when using the first definition. This problem of duality—amphetamine is both a therapeutic agent and a drug of abuse—permits a range of doses where the first definition may be true while the second is false. This is an issue for policy makers to muse over. Until that is settled (and accepting the section heading) I think "overdose" should be used carefully and sparingly, with parenthetical explanation considered.

The remainder of this sentence and remainder of the paragraph covers the same material covered in the addiction section that follows and should be incorporated into that section.

Since the synonyms phenylisopropylamine and benzyl methyl carbinamine are appropriate to place in the infobox, they may be mentioned here but elaborated in the history & culture article. The split article isn't reason to discriminate synonyms or summary mention here, and segregate them there. This editor removed my edit, added benzyl methyl carbinamine to the history article and tells me, "I'm hoping this addresses your concerns." I'll momentarily digress from dispute resolution etiquette—no one likes being treated in a patronizing manner. This editor made the move after a 3rd editor conditionally supported the inclusion of benzyl methyl carbinamine. At this point, given protocol, I should add phenylisopropylamine and benzyl methyl carbinamine until reasonable resolution occurs.

The split history article is entitled, "History and culture of substituted amphetamines". The term "substituted amphetamines" is esoteric to a general audience. It is contrary to the definition expressed in established medical references and commonly used at that level. It is particularly problematic because this history article is specific to amphetamine and methamphetamine, while substituted amphetamines—when used in medical literature—commonly refers to MDMA and similar psychedelic amphetamines. As such "substituted" should be removed from the title.

It is difficult to resolve this honorably because the response I received concerning my previous extensively cited presentation against "substituted" elicited a complaint about the length, particularly counting the individual characters in my post, seemingly because that editor had already made the final determination. Of course Wikipedia doesn't work this way. So despite chemists' association conventions, we must communicate to a general audience, and even a general medical audience, with definitions in wide use, careful to not confuse general readers. (WP:COMMONNAME) Forcing technical naming conventions obscure to common current use is a disservice. "Substituted" creates ambiguity. Unless there is some solid reason to the contrary, refuting the posted/quoted citations, I would like to move the article, truncating "substituted" from the title. — Box73 (talk) 09:08, 23 January 2016 (UTC)

Can you reword your concerns as bullet point sentences instead of paragraphs? I don't really want to read the blob of text above. I reverted your edit because you moved a paragraph that was requested in an FA discussion. I don't really care for the trade name parameter. Seppi333 (Insert 2¢) 11:05, 23 January 2016 (UTC)

Please understand that I’m doing what you asked as an act of goodwill.

• My trade names edit was appropriate but it was deleted without comment. Not caring for it isn’t a valid reason.
• The "Summary of addiction-related plasticity" template belongs in the addictions article but is superfluous here. A third of the columns are not mention in this article. Another is mentioned once. This template is seeded all over Wikipedia—in at least 13 different articles. It is beyond the scope of amphetamine.
• The “Addictions glossary” belongs in the addictions article. Almost half of the items don’t even exist here. Four occur once. The template is superfluous and beyond the scope of amphetamine.
• Your statement “Individuals who frequently overdose on amphetamine during recreational use have a high risk of developing an amphetamine addiction, since repeated overdoses gradually increase the level of accumbal ΔFosB, a "molecular switch" and "master control protein" for addiction.” Isn’t supported by the citations. One author says instead that addiction is a cause overdose, not the other way. When your cited sources use the substance abuse definition of overdose, you should use the therapeutic definition of OD. (see above).
• The rest of this (sentence and) paragraph belong in the addiction section below. They are redundant.
• The synonyms I added, phenylisopropylamine and benzyl methyl carbinamine, are significant. Historical significance doesn’t segregate them from the drug infobox to the history page you split off. A 3rd editor supported the inclusion of BMC. Removing my edit, moving it there, and telling me that you hope this addresses my concerns, doesn’t. The primary article infobox serves as a façade for the entire topic. I don’t feel this is how we should resolve disputes and I feel patronized.
• I want to move the "History and culture of substituted amphetamines" article you split off, removing “substituted”. In summary, “substituted amphetamines” is a systemic term of chemists, but not a common term to a general audience. To a medical audience “substituted amphetamines” commonly refers to psychedelic amphetamines like MDMA. We need to communicate to a general audience using a common term. (WP:COMMONNAME) My reasoning has previously been extensively cited, quoted and discussed. Other Wikipedia articles use amphetamines (eg, psychoactive drugs). I wanted to offer notice before making the move.

You deserve much credit for contributions to this article and others. Regardless of contributions and differences in opinion we all deserve respect, a positive attitude and constructive interaction. It seems impossible to resolve this ourselves without digression. — Box73 (talk) 14:32, 23 January 2016 (UTC)

We can add tradenames to the trade name parameter; alternatively, we can add a section link to the trade names section. The parameter wasn't meant to be used for a list of names. I'm opposed to listing individual drug names in this parameter when we have an entire section on this. Nevermind, I did both; they're listed now. Seppi333 (Insert 2¢) 18:05, 23 January 2016 (UTC)

That addiction template is directly relevant to the article because a column of data covers amphetamine's effects; the article text even references another one of the template columns in its discussion of treating amphetamine addiction.

I'm confused as to how you believe that sentence means repeated overdose is an effect as opposed to a cause of addiction. The 1st sentence of the 2nd reference supports that statement for all drugs, substituting the term "exposure". The remainder of that paragraph was requested in FA by an editor who wanted a summary paragraph of the addiction section.

I'm opposed to adding "benzyl methyl carbinamine" and "phenylisopropylamine" to the infobox. The infobox isn't a place to dump a large list of names and synonyms so stop trying to use it like that. The synonyms note was meant to serve that purpose.

If you want to move the substituted amphetamines articles, then you should be going through WP:RM for community discussion, not this talk page.

Seppi333 (Insert 2¢) 17:50, 23 January 2016 (UTC)

Benzedrine and article ownership

Benzedrine is an established legacy brand fixed in popular vocabulary. It appears in dictionaries. An encyclopedia is comprehensive in terms of information, so this is appropriate. You seem unwilling to participate in a constructive dialogue with me, feel it is a burden to you, but engage in edit warring. This goes beyond this matter and it is difficult not to react. We need outside resolution. — Box73 (talk) 18:07, 24 January 2016 (UTC)

How does any of that merit placing a non-current brand in a drugbox field right next to current trade names? Seppi333 (Insert 2¢) 18:17, 24 January 2016 (UTC)

On the flipside, ref #1 lists over a dozen obsolete amphetamine brands. If you place Benzedrine there, why shouldn't we flood the parameter with all of those? Seppi333 (Insert 2¢) 18:19, 24 January 2016 (UTC)

Because that would overwhelm the field AND those brands aren't notable. Alternatively, consider amitriptyline and doxepin. Elavil and Sinequin (respectively) are listed but both brands are non-current.

I get your reasoning and desire to keep this focused. Benzedrine belongs because it is firmly established in our vocabulary. It is listed in Oxford and Merriam-Webster Dictionaries. It surfaces in the 2012 Atlantic article, The Lost World of Benzedrine and a 2010 Medical Humanities article, Thrills, spills and pills: Bond, Benzedrine and the pharmacology of peace among others. None of this is true of Alentol, Psychoton or Simpamina. Even though Benzedrine is no longer made, this makes it a special case belonging there. Is there a way to distinguish it in the list without causing clutter or undue attention? — Box73 (talk) 21:00, 24 January 2016 (UTC)

Your two examples are not featured articles, so they don't set the precedent for this article. Beyond that point, Elavil is a current trade name in Canada, but not the US. I have no clue about Sinequin for doxepin, but it is marketed worldwide. In any event, I don't think obsolete trade names belong in the trade names field. If you really want to push the issue, it should be raised at template talk:Infobox drug for wider input. Seppi333 (Insert 2¢) 21:58, 24 January 2016 (UTC)

I came to this article via Benzadrine, trying to get a history of "Bennies," my interest piqued by their heavy use in detective fiction set in the 40s and 50s. And I find an article that breaks down the internals, but has no specifics about anything related to Benzadrine in particular. It's apparent to many in terms of historical relevance, but I find obstinance to providing relevant information going on in the talk page. It deserves its own page and is a subject of interest. Spawn777 (talk) 21:59, 27 February 2016 (UTC)

@Spawn777: History of Benzedrine. Seppi333 (Insert 2¢) 07:29, 28 February 2016 (UTC)

@Seppi333: Turns out I can't spell. I wonder if the spelling error ,"benzadrine", should route to that page, however or do at the very least do a regular search so that page can be discovered Spawn777 (talk) 01:38, 29 February 2016 (UTC)

This page links to that article in two of the three instances where "Benzedrine" is listed in the text, including in the lead. I expect people will end up there if they're looking for information about benzedrine on this page. Unfortunately, I can't think of an encyclopedic redirect to that title that starts with "Benzedrine". Seppi333 (Insert 2¢) 01:49, 29 February 2016 (UTC)

Elevating amphetamine from notes

Because of the widespread use of amphetamines as the popular name of the class, I noted this in the text (lead) itself. This is necessary, and a reasonable but minimal compromise if substituted amphetamines (SA) is used generally. Further the footnote only justified the use of SA not stating the amphetamines is also the class name. I have previously provided overwhelming support for amphetamines as the class with little or no contrary reliable sources, simply opinion. If we use SA, can't we elevate the matter above a vague footnote. It exists in the body but some mention should exist in the lead.

Re the lede and History, society, and culture: Benzedrine Sulfate had the wide application of use, not Benzedrine inhalers.

Lastly, in Summary of addiction-related plasticity: Type of reinforcer, the category opiate might be changed to opioid. The effects likely apply to all MOR agonists. — Box73 (talk) 00:49, 7 March 2016 (UTC) revise — Box73 (talk) 01:42, 7 March 2016 (UTC)

I don't know how many times I need to hammer this point in: "amphetamines" and "substituted amphetamines" ARE NOT THE SAME THING. Covering the sulfate in the history section is fine, especially since you actually cited it. The lead didn't need to be changed to reflect what you wrote there, as it's correct as is. The column entry in that plasticity table is consistent with the ref, which is what matters. Seppi333 (Insert 2¢) 12:11, 7 March 2016 (UTC)

I appreciate the clarity: "amphetamines" and "substituted amphetamines" are not the same thing. And we're not defining this internally—not by Wikipedia itself. Amphetamines are a class of drugs related to amphetamine including amphetamine and methamphetamine. I will cite it momentarily; if one or two reliable sources aren't sufficient I'll provide 50 citations if you wish. (But then WP:VERIFY doesn't require the obvious be cited.) Then I argue: this widely used drug class needs to be included as well as the chemical class. The footnote needs to change because it doesn't distinguish drug class from chemical class. This will be accurate and neutral.

No the lead isn't correct. Benzedrine inhalers were nasal decongestants. Benzedrine tablets and elixir, which were called Benzedrine Sulfate, were used for a variety of conditions: such as epilepsy, myasthenia gravis, infantile cerebral palsy, morphine addiction, codeine addiction, alcoholism, post-encephalitic parkinsonism, night blindness, restless legs and thirty more. Benzedrine inhalers were not used for narcolepsy, obesity or ADHD in children, but Benzedrine Sulfate was. Cut inhalers and the statement is acceptable. If some reference says Benzedrine was used for a variety of conditions, it is referring to the sulfate salt (or some other formulation) not the inhaler. SKF used "Benzedrine Sulfate" to distinguish it from "Benzedrine", but because the salt (especially the tablets) was available after the inhalers were discontinued, this was then called Benzedrine. Feature article-wise, where is inhalers being used for a variety of conditions cited?

re opioid, I'm just giving you something to consider, they are not personal criticisms... Opioid is the preferred term for all MOR active drugs. Opioid includes opiates. Are these effects only true for drugs derived from opium? Not fentanyl for example? There is a difference between being accurate and being literal. (Similarly, why isn't craving included in the addiction definition?)

I've gained a respect for you and your contributions. I see how much improvement other med/pharm articles need in quality and adherence to MOS. Having said that I wasn't aware that you wrote the article or are now the gatekeeper of standards WP:OWN. It now belongs to Wikipedia. Let's work on this as though it's a community project seeking a neutral point of view. BTW, why does that citation needed tag exist? — Box73 (talk) 22:20, 7 March 2016 (UTC)

• The reason why the lead never mentioned the term "amphetamines" is two-fold: 1) the "amphetamines" class is stupidly difficult to define in concrete terms while an easily definable (literally only need 1 sentence) subclass exists; and 2) the only times when an amphetamine drug class needed to be mentioned in the body were in contexts which were relevant only to its structural derivatives. Now, with that said, is there any particular reason why you want to introduce a term that would require like a paragraph to clearly define? You realize "amphetamines" includes basically all selective and nonselective norepinephrine reuptake inhibitors and/or releasers, DA reuptake inhibitors and/or releasers, 5-HT reuptake inhibitors and/or releasers, direct agonists of monoamine receptors, and even other less related functional analogs? Hell, I've even seen caffeine called an "amphetamine" in a paper that I've cited on wikipedia, and caffeine's pharmacodynamics are 100% distinct from amphetamine's; there isn't a single biological target in common between the two drugs. They merely act on receptors within some of the same neural pathways within the brain and happen to have similar "psychostimulant" effects as a result.(struck out since I can't seem to find the paper I mentioned) With all that said, I really don't see any usefulness and I do see a lot of unnecessary work from trying to cover the "amphetamines" drug class in this article. If the term actually was (and needed to be) used in the body of the article, then I'd reconsider defining the class in the article. Merely saying "amphetamine is part of class X" without defining "class X" in concrete terms is wholly pointless though because the statement is too vague to be useful to an uninformed reader. Lastly, "substituted amphetamines" are a drug class as well as a structural class: the former concept encompasses the latter. EDIT: the quote in this ref is equivalent to the MESH definition that is used for pubmed indexing, which defines "amphetamines" as "analogs or derivatives of amphetamine".

In a nutshell, it simply needs to be acknowledged upfront and nothing more.

There isn't a single conventional precise definition of amphetamines (class), particularily the bounds, but reliable sources continue to use the term to include d,l-amphetamine, d-amphetamine and d-methamphetamine, or more generally the racemates and enantiomers of amphetamine and methamphetamine. While MeSH may catagorize congeners such as pramipexole, atomoxetine or tapentadol as amphetamines, no academic writing I know of does; indeed MeSH is a also a thesaurus. (Re quote in this ref) I suggest Yoshida's first or second definition for amphetamines (plural form, ¶4 below), but less than the broadest context. Here's Yoshida's full quote:

Amphetamine, in the singular form, properly applies to the racemate of 2-amino-1-phenylpropane. The molecule of amphetamine has one asymmetric carbon, yielding two optical isomers. The spelling of its English INN (International Nonproprietary Name) is amfetamine (WHO, 1992a). The INNs are a standard drug nomenclature consisting of generic names of pharmaceutical substances determined by WHO (the World Health Organization) in order to help avoid confusion with regard to the identity of pharmaceutical substances. INNs are indicated in parentheses the first time they appear in this chapter in order to facilitate cross-referencing.
Dexamphetamine (INN: dexamfetamine) is the dextro rotatory or (+)-isomer of amphetamine. Since the (+)-form is known to be significantly more potent than the levo-form, amphetamine, which is the mixture of the same quantity of dextro- and levo-forms, is less potent than dexamphetamine.
Methamphetamine (INN: metamfetamine) is the N-methyl derivative of amphetamine. Unlike amfetamine (INN) which corresponds to the racemic mixture, metamfetamine (INN) refers to the dextro-isomer of l-phenyl-2-methylaminopropane. Methamphetamine is more potent than dexamphetamine.
Amphetamines, in the plural form, usually applies at least to the above three substances. In this chapter, the term amphetamines will be used in this sense. Some people include, in addition, levamfetamine [INN] the l-form of amphetamine, as well as levomethamphetamine and methamphetamine racemate or, in other words, all stereoisomers of both 2-amino-1-phenylpropane and 2-methylamino-1-phenylpropane. In its broadest context, however. the term can even embrace a large number of structurally and pharmacologically related substances. In this chapter, some of these amphetamine analogues are briefly mentioned under amphetamine-like substances.

Obviously the quote in the ref will need to be revised since "term" does not refer to the singular "amphetamine". Having said that, I totally agree, the term is becoming too muddy for general use. /more

If you consider that the plural form of the word isn't used for grammatical reasons when terms like "neurotoxicity", "dependence", "addiction", "use disorders", etc., are appended to "amphetamines" and refer to "amphetamines" in general, you'll understand my reasoning for quoting it like that. Unique definitions for the term "amphetamines" necessarily apply to the singular "amphetamine" solely because of that grammar point. In any event, I think it's fine to add the more restricted definition of the term "amphetamines" that you noted to the article, since it's just a 1 sentence definition. I'll add it shortly. Seppi333 (Insert 2¢) 15:44, 8 March 2016 (UTC)

I added content on the amphetamines definitions and clarified the quote that you wanted: special:permalink/709003556#cite_note-50. I added all of the content to the note attached to the substituted amphetamines class because I couldn't figure out an encyclopedic and fluid way to introduce it into the lead text without placing the existing text from the note in that paragraph in the lead along with it. The text that was already in that note shouldn't be anywhere in the lead/body of the article because it's literally a comment on the article itself (it wouldn't be encyclopedic). I thought it read rather awkwardly when I included the various definitions of the "amphetamines" class in that paragraph and then immediately followed it with the note stating that the article won't use the term "amphetamines" this way. I actually think keeping the new material and the statements that were originally in that note together illustrates the motivation for creating that note and explicitly clarifying/defining the compounds to which amphetamine(s)/"substituted amphetamines" refers in the article. I'm not sure how you feel about it this approach, but if you feel that the new content on the amphetamines class covered outside of the note; the best place would be in the chemistry section of the article instead of the lead, since 1/2 a lead paragraph is rather excessive lead coverage of something which isn't mentioned in the body (WP:LEAD#Relative emphasis). Doing this would require revising the existing text in that note though. Seppi333 (Insert 2¢) 17:46, 8 March 2016 (UTC)

• The inhalers were initially used for colds, asthma, and nasal decongestion; only the use as a nasal decongestant panned out clinically.[4] I have no clue what "off-label" uses it may have had, which is hinted at by the marketing of the inhaler to the general public. This much newer review which was already cited in the article also cites exactly the same content you added from a 7 decade old paper. In any event, I don't particularly care enough to argue about the change to that sentence in the lead, so we'll have it your way and cut the word "inhaler".

I hadn't considered the premarketing trials of the base. The condition that Rasmussen missed was in epilepsy, to offset sedation from phenobarbital. /more

• The review that the table cites uses the words "opiate" and "opioid" repeatedly. My guess for why he used the term "opiate" instead of the more general term "opioid" in the table would be the same reason I didn't generalize template:psychostimulant addiction to encompass methylphenidate and cocaine: there are small but notable differences between amphetamine and its immediate analogs and pure dopamine reuptake inhibitors in some forms of addiction-related plasticity. Perhaps there are similar differences between opiates and at least a few members of the more general class of opioids? Maybe the primary sources which he cited in constructing the table were all relevant to opiates? I can't say, since I haven't spent much time researching opioid-induced plasticity or checked the table refs from that review. I'm not inclined to generalize it simply due to general pharmacodynamic similarities for the aforementioned reasons though.

There's some disagreement about what qualifies as an opiate too. Interesting about the DA releasers and uptake inhibitors differences. /more

WRT the term "craving", it's not covered because the current description of an addiction is accurate even without covering cravings (cravings arise from the rewarding property of a drug and are somewhere between ΔFosB overexpression and compulsive drug use in a long chain of cause and effect, as described below) and tying the concept of craving into the existing text would require even more complicated coverage in the mechanisms section. For example, how ΔFosB is responsible for "reward sensitization" (this is really the sensitization of incentive salience, or pathologically amplified "wanting", to be precise), what this "reward sensitization" actually means, involves downstream from ΔFosB at a molecular level, and how it relates to positive reinforcement and increased drug self-administration: otherwise neutral and even non-rewarding stimuli become drug cues which function as secondary reinforcers due to associative learning; these cues then get assigned their own "incentive salience"/"want" that, in turn, transfers to and facilitates excessive "wanting" (cravings) for the primary reinforcer (the addictive drug) that it was associated with. This pathologically amplified "wanting" for an addictive drug is a drug craving and it is the immediate cause of compulsive drug use in drug addicts. I've only recently finished covering this relationship in generality in the addiction article (see reward sensitization), so it's not surprising that addiction-related cravings are not covered here. I don't think the relationship is explained very well in that section at the moment since it currently involves a lot of jargon.

Thank you. I'll need to look at this again. The craving is rather like the obsession to the compulsion of drug use. I wonder what the evolutionary function of this ΔFosB mechanism is (the liability) and a relationship to oxytocin as maternal bonding or love generally shares characteristics of addiction. /more

• Yes, I did essentially (re)write the article, with the exception of the chemistry section which Boghog wrote due to my general lack of familiarity with organic chemistry & chemical synthesis. This isn't a claim of ownership (which isn't relevant to WP:OWN anyway - that policy concerns editing behavior, not statements on a talk page); it's simply a fact which is reflected in my text contribution to this article, which is greater than the current text size of the article (as of this edit: current size: 188,400 Bytes; my contribution: 193,265 Bytes). Seppi333 (Insert 2¢) 01:24, 8 March 2016 (UTC)

With almost every med/pharm article I visit I see blatant MOS issues and I appreciate the quality of amphetamine. If you need the number for poison control US/UK it's listed at nortriptyline. Unbelievable. — Box73 (talk) 11:49, 8 March 2016 (UTC)  — Box73 (talk) 12:43, 8 March 2016 (UTC)  — Box73 (talk) 12:57, 8 March 2016 (UTC)

@Box73: I just want to clarify one issue. I have no problem at all with you adding content to this article. I really don't. But when new material is added to the article, or existing content is substantively changed (i.e., when content is changed so that its current sources don't directly support all parts of the statement anymore), sources must be cited, especially if the content is a medical claim. That's not something I can compromise on because it's mandated by both WP:MEDRS and the WP:featured article criteria. I had to spend a great deal of time ensuring that the high citation standards of both those policies were met when I wrote this article and took it through the featured article process, and this is why I've been insisting that new content in this article also meets these standards. That said, I'd be perfectly content with any addition you make as long as you maintain the quality of the article when you do it. Adding and citing the benzedrine sulfate statement is a perfect example of what I'd consider a good addition to this article. Seppi333 (Insert 2¢) 17:33, 7 March 2016 (UTC)

Picture of structure in infobox

Wouldn't the structure of amphetamine be more accurately drawn as this to indicate that it exhibits stereoisomerism? Also, to keep in line with most other chemical structures that appear in WP infoboxes, the CH3 shouldn't be explicitly written out - it doesn't need to be. Illini407 ^talk 19:06, 19 March 2016 (UTC)

@Boghog: This is really your area. Seppi333 (Insert 2¢) 22:24, 20 March 2016 (UTC)

Thanks for the heads up Seppi333. From the WP:Manual of Style/Chemistry/Structure drawing:

• For articles on racemates, the stereochemistry should be depicted as undefined (straight and not wavy nor wedged bonds attached to the stereogenic center).
• The use of explicit methyl groups in the following cases is a stylistic choice, and both forms are generally acceptable on Wikipedia:

The MOS is clear that straight and not wavy lines should be used depict the stereochemistry of racemates. The terminal CH₃ is a stylistic choice. I prefer it because I think it is clearer/less ambiguous. Boghog (talk) 05:55, 21 March 2016 (UTC)