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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.
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
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)
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)
@
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)
@
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)
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)
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)
Routes of administration: Since Benzedrine inhalers are long gone, nasal inhalation should be eliminated from Medical, or somehow qualified.
Metabolism. I'm confused between "amphetamine only" and "other". Does "other" mean active metabolites?
Onset of action: This gets into medical vs recreational distinctions as well as site of action (central vs nasal).
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).
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.
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.)
"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 [1]
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 [2]
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 [3]
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 [4]
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 [5]
A Penn State Dept. of Chemistry PowerPoint presentation includes a slide graphic [6] 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... [7] 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.
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. [8] [9] 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. [10] 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." [11] 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.
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)
Reflist
|
---|
References
|
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". [1] 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. [2] Wide usage exists in early medical literature—secondary sources concerning the name. [3] [4] [5] [6] [7] [8] [9] 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. [1] [10] [11] (β-phenylisopropylamine was another early term encountered. [12])
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)
References
{{
cite book}}
: CS1 maint: multiple names: authors list (
link)
"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)
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)
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)
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)
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.
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)
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:
![]() | This is an archive of past discussions. Do not edit the contents of this page. If you wish to start a new discussion or revive an old one, please do so on the current talk page. |
Archive 1 | ← | Archive 4 | Archive 5 | Archive 6 | Archive 7 | Archive 8 |
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.
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
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)
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)
@
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)
@
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)
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)
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)
Routes of administration: Since Benzedrine inhalers are long gone, nasal inhalation should be eliminated from Medical, or somehow qualified.
Metabolism. I'm confused between "amphetamine only" and "other". Does "other" mean active metabolites?
Onset of action: This gets into medical vs recreational distinctions as well as site of action (central vs nasal).
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).
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.
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.)
"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 [1]
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 [2]
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 [3]
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 [4]
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 [5]
A Penn State Dept. of Chemistry PowerPoint presentation includes a slide graphic [6] 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... [7] 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.
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. [8] [9] 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. [10] 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." [11] 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.
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)
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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". [1] 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. [2] Wide usage exists in early medical literature—secondary sources concerning the name. [3] [4] [5] [6] [7] [8] [9] 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. [1] [10] [11] (β-phenylisopropylamine was another early term encountered. [12])
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)
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"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)
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)
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)
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)
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.
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)
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: