Talk:Amphetamine

Re

@Doc James and Casliber: Would like your feedback on Amphetamine#Pharmacomicrobiomics; pinging you two since you recently took an interest in this article. Only the second paragraph is technically "on topic" and within the article's scope, but the 2nd paragraph almost seems like trivia without a contextual understanding, which is what the first paragraph provides: it states the types of clinically significant drug-microbiota interactions. Really just looking for general feedback, but also wondering whether you think this particular statement from the 1st paragraph is worth keeping or cutting: The nascent and active field of research on drug-microbe interactions – known as pharmacomicrobiomics – lies at the intersection of systems microbiology, genomics, systems pharmacology, and personalized medicine.

@AmericanLemming: If you could proofread/copyedit this section like you did with the other technical ones during the FAC review, I'd greatly appreciate it. I did my best to make it accessible, but I think you might be a better judge of what is/isn't understandable to a layperson than me for this topic. Seppi333 (Insert 2¢) 16:37, 5 August 2019 (UTC)

I agree that the first paragraph is too off-topic to include. I'd remove it. Cas Liber (talk · contribs) 20:34, 5 August 2019 (UTC)

I also agree with removing that paragraph due to it being off topic. Doc James (talk · contribs · email) 04:04, 7 August 2019 (UTC)

Initial comments

1. I agree with CasLiber that the first paragraph is a bit off-topic; the information there probably fits better in the main pharmacomicrobiomics article.

2. Also, it would be helpful to briefly explain the significance/implications of this study; for example, do the authors think that differences in the microbiome between individuals might explain some of the differences in how they respond to amphetamine?

3. I noticed that the link for tyramine oxidase redirects to the article on monoamine oxidase; is this bacterial enzyme analogous to human monoamine oxidase?

That's all for today. AmericanLemming (talk) 01:05, 7 August 2019 (UTC)

Re 1&2: Excluding the statements in the note and the first sentence about microbial and human genomes, everything in the first paragraph is mentioned in that study; the clinical significance of the finding is also mentioned in the paper, but I figured that since it's a primary source, I probably shouldn't be using it to cite a clinical claim. In a nutshell, the clinical significance is that E. coli can affect amphetamine's pharmacokinetics (its oral bioavailability and its metabolism) and variations in gastrointestinal E. coli colonization/concentration between individuals explains some of the inter-individual variation in amphetamine's clinical response (very high prevalence of E. coli in the gut → reduced clinical efficacy relative to people with normal [low] amounts of E. coli in the gut). It goes on to discuss the use of the findings in redesigning the drug (see the quote below or read the end of the paper here: sci-hub.tw/10.1002/jcb.28396); however, I don't think the authors knew that amphetamine's prodrug (lisdexamfetamine) isn't converted into dextroamphetamine until it's absorbed into human blood plasma, which is (normally) sterile. I don't think it's likely that lisdexamfetamine would be metabolized by E. coli's tyramine oxidase due to the sizable difference in the chemical structure, but I may be wrong. @Doc James: do you think I should just cite the paper for the clinical statements?

Re 3: the tyramine oxidase they're referring to is the tyramine oxidase encoded by E. coli's tynA gene (this isn't mentioned in the paper, but they refer readers to expasy.org, which after navigating through the cross-links, one can find that tynA is listed as the encoding gene for E. coli's tyramine oxidase; also, the tyramine oxidase for one of the E. coli strains (i.e., MS 116‐1) that were mentioned in the paper (strains ATCC 8739, HS, MS 116‐1, MS 146‐1, MS 175‐1) on NCBI Protein is listed as being encoded by tynA). The correct article on this would be primary amine oxidase (per the NCBI Protein link, [1], and the UniProt entry for tynA in E. coli) since that's the name of the protein that tynA encodes and the fact that we normally use protein names as article titles.

Tangential point: Based upon the reaction that tyramine oxidase catalyzes (i.e., RCH₂NH₂ + H₂O + O₂ $\rightleftharpoons$ RCHO + NH₃ + H₂O₂) and more specifically the fact that tynA metabolizes phenethylamine into phenylacetaldehyde and tyramine (4-hydroxyphenethylamine) into 4-hydroxyphenylacetaldehyde (I created this article today due to the number of red backlinks; the metabolic pathway I'm talking about here is now covered in that article), E. coli would seem to metabolize amphetamine into alpha-methylphenylacetaldehyde (which is probably further metabolized by E. coli's feaB enzyme into a methylated derivative of phenylacetate, based upon the metabolic fate of phenylacetaldehye and 4-hydroxyphenylacetaldehyde in E. coli - this pathway is covered in the UniProt link); that compound isn't naturally produced by any human enzymes. I obviously can't state any of this in the article since I can't (yet) cite a paper that explicitly covers it. Seppi333 (Insert 2¢) 11:31, 7 August 2019 (UTC)

Edit: I fixed the tyramine oxidase link in the article and mentioned tyramine oxidase/tynA in primary amine oxidase. The tyramine oxidase redirect is probably correctly targeted since I'm fairly certain that synonym maps either to the human MAOA gene or both human MAO genes. Seppi333 (Insert 2¢) 05:16, 8 August 2019 (UTC)

Is this clinically important. Doc James (talk · contribs · email) 13:55, 8 August 2019 (UTC)

Yes, and this information can be used clinically in any doctors' office that can test for microbial concentrations of specific strains of bacteria (which admittedly is very few at the moment, as it would require employing the same molecular biology techniques as required for diagnosing small intestinal bacterial overgrowth - i.e., gut fluid aspiration and a microbiological culture). Seppi333 (Insert 2¢) 03:58, 10 August 2019 (UTC)

References

Follow-up comments

I’m pretty satisfied with the section as a whole; I just have some suggestions for replacing some technical language with simpler language that conveys largely the same meaning.

4. In the first paragraph, it says “Homo sapiens cells”; I would just call them “human cells”.

5. Also, I think it would still be a good idea to give a brief definition of what “pharmacomicrobiomics” means and link to the article on it. I suggest something like “there is considerable potential for interactions between drugs and an individual's microbiome. The study of these interactions is called pharmacomicrobiomics, which include drugs altering the composition of the human microbiome…”

6. As for the second paragraph, we should probably link promiscuous metabolism (needs to be piped) and include a brief definition in a footnote, since I don't feel that the introduction to the Enzyme promiscuity article is all that helpful for a non-expert like me.

7. Replacing human gastrointestinal microbiota with “gut bacteria” would probably be an oversimplification, but if bacteria are mainly responsible for drug metabolism by microbes, could we put say “primarily bacteria” in parentheses afterward?

8. Also, replacing “into blood plasma” with “into the blood” would sacrifice a little precision but would be a little simpler. AmericanLemming (talk) 03:03, 13 August 2019 (UTC)

@AmericanLemming: Sorry about the long delay in my reply; I'd meant to respond earlier but was tied up at the time and forgot about it in the meantime.

4.  Done

5.  Added at the end of the first paragraph: "The field that studies these interactions is known as pharmacomicrobiomics."

6. I think what the authors meant here was that amphetamine is likely a ligand for (i.e., likely metabolized by) many currently unidentified microbial enzymes, not that the enzymes themselves are promiscuous.

7.  Done

8.  Done - changed it to "into the blood stream"

Seppi333 (Insert 2¢) 12:07, 16 August 2019 (UTC)

@AmericanLemming: Thank you for reviewing that for me! Seppi333 (Insert 2¢) 06:34, 18 August 2019 (UTC)

I find this page to be biased in the emphasis on how safe amphetamines are and that when abused then there are problems. Many people end up with issues at prescribed doses such as withdrawal and dependence which can also be found in research. Mentions how younger kids are less likely to abuse drugs later on in life if they start on amphetamines at a young age. What is skipped is that starting at any other age increases the chance. Ignores acute tolerance which happens within hours of taking the medication and was used to base the design of various extended release products. Ignores many harmful aspects such as oxidative stress, downregulation of receptors and the production of neurotransmitters, neurotransmitter depletion, Instead it only mentions pathways to addiction. Dependence is related, but not mentioned when the brain no longer efficiently manages it's own neurotransmitters and has to rely on the medication to do it. Even at low doses people often feel the Adderall crash when it wears off. All be it mildly. Feels like every section has to say something about it's safe at prescribed doses or implies negative outcomes only for abusers. Seems more like damage control and people trying to sell me on the idea. Safety and what not should be in one section, not in every section as if trying to protect peoples perceptions. Not a single mention of the effects on the endocrine system. Skipped the issue on stunted growth all together. etc. Aside from that, very informative. — Preceding unsigned comment added by 69.248.160.198 (talk) 10:32, 9 April 2023 (UTC)

I don't 🤷 Strawkipedia (talk) 06:29, 8 July 2023 (UTC)

WP:FACR: 2c

@Headbomb: You updated 2 page ranges, added 2 pmcs, added 3 issues, and added a missing year in [2]; those were the useful revisions. Meanwhile, you changed some of the abbreviated journal titles to full titles, while leaving e.g., references 101, 102, 103, and 105 abbreviated. All of the journals were consistently formatted before you used a bot to bork the citation formatting (which is why those bots were denied from editing this page before you removed them from the template). You need to consistently format the journal titles in this article or I'm going to revert your edit. It's not my job to clean up after bot edits that inconsistently revise this page's citations. Seppi333 (Insert 2¢) 20:06, 24 December 2019 (UTC)

Should be fixed now. Citations were located in different templates. Headbomb {t · c · p · b} 20:17, 24 December 2019 (UTC)

6, 8, 11, 184, and 188 are all still "J. soandso." Seppi333 (Insert 2¢) 20:35, 24 December 2019 (UTC)

Same reason. Done. Headbomb {t · c · p · b} 20:55, 24 December 2019 (UTC)

@Headbomb: Thanks. With that fixed, your revisions were rather helpful overall. Seppi333 (Insert 2¢) 23:24, 24 December 2019 (UTC)

Abbreviations

Resolved

@Seppi333: It isn't clear if MOS:FIRSTABBR should apply to citations since they stand alone in their usage. For example, there is no problem with repeating the same link in many citations within an article MOS:REPEATLINK. Whywhenwhohow (talk) 06:22, 25 December 2019 (UTC)

@Whywhenwhohow: I'm familiar with the exception for links in citations; I simply dislike them. When I click something in a citation, I expect to navigate outside WP, not internally. Ignoring the guideline entirely, an abbreviation for a website or publisher entry is just extraneous markup; it doesn't serve any purpose like it does in the article text.

Anyway, can you restore the publisher parameters in the citations to the FDA website that you changed to DailyMed? It should be listed as the manufacturer; regardless of what website hosts the prescribing information, the publisher would still remain the same. I already restored a few, but there's others that need to be fixed. Seppi333 (Insert 2¢) 06:58, 25 December 2019 (UTC)

Yes, but why do you prefer the ones from the FDA website? They are PDF format and harder to navigate? The NIH DailyMed website is the official provider of FDA label information Whywhenwhohow (talk) 08:27, 25 December 2019 (UTC)

I don't have a fixed preference for DailyMed or the FDA's labels as a citation since both have an advantage over the other; the actual content is identical though. The PDFs have page numbers which makes verifiability easier when the prescribing information is rather long, but DailyMed is easier to navigate given its design. I'm just used to citing FDA labels since I've always used Drugs@FDA to search for drug information (e.g., the label itself, approval data, and information on current/actively marketed brands as well as discontinued drug products associated with the active ingredient I'm searching).

In any event, I just realized that I worded my earlier request about the publisher information very poorly; what I meant to say was to restore the publisher parameters from the FDA citations in the DailyMed citations. Databases like Drugs@FDA and DailyMed that host a drug label online should always just be listed in the website/work parameter of {{cite web}}, so you were doing that part correctly. The publishers are the entities that write/edit and produce a document, which in this case is the prescribing information − i.e., pharmaceutical companies like Shire Plc, Hoffmann-La Roche, Merck & Co, etc.. While the FDA approves prescribing information for drugs, the drug label for any given drug is the copyrighted intellectual property of the manufacturer/pharmaceutical company that produces the drug because they're the authors of the corresponding drug label; that's why they're listed as the publisher for drug labels. I've added the original citation templates below as an example. In any event, I'll go ahead and fix the DailyMed citations since you already spent time actioning my poorly worded request. Seppi333 (Insert 2¢) 09:59, 25 December 2019 (UTC)

They're all fixed now. If you want to change the 2 FDA drug label citations I added to DailyMed citations, feel free to do so. I don't really care which one we use. Seppi333 (Insert 2¢) 10:19, 25 December 2019 (UTC)

Drug label citation templates

{{cite web|title=Adderall IR Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2015/011522s042lbl.pdf|publisher = Teva Pharmaceuticals USA, Inc.|work = United States Food and Drug Administration|date=October 2015|accessdate=18 May 2016|pages=1–6}} {{cite web|title = Adderall XR Prescribing Information|url = www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf|page = 11|publisher = Shire US Inc.|work = United States Food and Drug Administration|date=December 2013|accessdate = 30 December 2013}} {{cite web|title=Evekeo Prescribing Information|url=www.evekeo.com/assets/evekeo-pi.pdf|publisher=Arbor Pharmaceuticals LLC|accessdate=20 July 2018|pages=1–2|date=September 2016}} {{cite web|title=Dyanavel XR Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/208147s003lbl.pdf|publisher= Tris Pharma, Inc.|work=United States Food and Drug Administration|accessdate=4 August 2017|pages=1–14|date=May 2017|quote=DYANAVEL XR contains d-amphetamine and l-amphetamine in a ratio of 3.2 to 1 ... The most common (≥2% in the DYANAVEL XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 108 patients with ADHD (aged 6–12 years) were: epistaxis, allergic rhinitis and upper abdominal pain. ... <br />DOSAGE FORMS AND STRENGTHS<br />Extended-release oral suspension contains 2.5 mg amphetamine base per mL.}} {{cite web|title=Vyvanse Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/021977s045,208510s001lbl.pdf|pages = 3–13, 17–21|website = United States Food and Drug Administration|publisher = Shire US Inc.|accessdate=10 July 2017|date = May 2017}} {{cite web|title=Mydayis Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/022063s000lbl.pdf|website=United States Food and Drug Administration|publisher=Shire US Inc.|accessdate=8 August 2017|pages=1–21|date=June 2017}} {{cite web|title=Adzenys XR-ODT Prescribing Information|url=www.accessdata.fda.gov/drugsatfda_docs/label/2017/204326s002lbl.pdf|website = United States Food and Drug Administration|publisher=Neos Therapeutics, Inc.|accessdate=10 August 2017|page=16|date=January 2017|quote = ADZENYS XR-ODT (amphetamine extended-release orally disintegrating tablet) contains a 3 to 1 ratio of d- to l-amphetamine, a central nervous system stimulant.}}

Page size

At 241,890 bytes of wiki markup, this page is far too large. That's particularly troubling for a page listed as a featured article. How can it best be divided? For example, splitting off the entire 'Pharmacology' section would remove over a fifth of that (less if a summary is kept here). Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 11:19, 2 January 2020 (UTC) @Pigsonthewing:

Document statistics:

File size: 989 kB

Prose size (including all HTML code): 123 kB

References (including all HTML code): 25 kB

Wiki text: 236 kB

Prose size (text only): 49 kB (6811 words) "readable prose size"

References (text only): 2506 B

User_talk:Dr_pda/prosesize.js

To quote WP:TOOBIG: These rules of thumb apply only to readable prose and not to wiki markup size (as found on history lists or other means), and each kB can be equated to 1,000 characters.

I'm not even going to consider splitting this article right now given that it's not even that long by the actual guideline metric. Seppi333 (Insert 2¢) 11:43, 2 January 2020 (UTC)

Wow, four bigs, and and underline? -- Mikeblas (talk) 19:56, 12 July 2020 (UTC)

"I'm not even going to consider..." That's OK, you're not required to participate. But in declaring that you're not participating, please don't selectively quite only parts of a guideline, as you do - unnecessarily garishly - above. The guidleline also says, near the top of the page (and so before the subsection you quote): "There are three related measures of an article's size: Readable-prose size [...] Wiki markup size [and] Browser-page size". Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 12:05, 2 January 2020 (UTC)

Yes, and the guideline says absolutely nothing about hard-limits on markup size like it does with the prose size, which you clearly are trying to use as a justification for splitting pages based upon their on markup size. The thing is, this page might have a markup size in the 200+kB range, but both this script and xtools indicate that the prose size is 49-50kB. No one is going to buy what you are selling if you keep trying to argue that this page needs to be split based upon markup size. And even if that was an issue, which it clearly is not, I could simply move this entire page's source code to a template and transclude it in, causing this page's markup size to drop to <10kB while the readable prose size remains the same. Seppi333 (Insert 2¢) 12:14, 2 January 2020 (UTC)

Not so; for example the guideline says: "The text on a 32 kB page takes about five seconds to load for editing on a dial-up connection, with accompanying images taking additional time, so pages significantly larger than this are difficult for older browsers to display. Some large articles exist for topics that require depth and detail, but typically articles of such size are split into two or more smaller articles. ". Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 12:21, 2 January 2020 (UTC)

I don't see a hard/fixed limit anywhere in the text you quoted. It appears to assert the incredibly obvious fact that shittier connections load webpages more slowly, and we're talking about two-tenths of one megabyte. Seppi333 (Insert 2¢) 12:26, 2 January 2020 (UTC)

Wikipedia talk:Article size is available, should you wish to dispute the contents of the guideline. Andy Mabbett (Pigsonthewing); Talk to Andy; Andy's edits 12:50, 2 January 2020 (UTC)

@Pigsonthewing: Dispute the guideline? Why would I do that? It supports my assertion and contradicts yours. I'm actually happy with it the way it is. Also, thank you again for the nomination. You're doing me a favor here. Seppi333 (Insert 2¢) 13:15, 2 January 2020 (UTC)

Transclusion

This article is a source for transcluded sections in Adderrall. Its a real house of cards -- reference definitions must be in certain spots, different sections are tagged with <noinclude and one article or another is often broken because of problems. Is transclusion really the best way to build these articles? -- Mikeblas (talk) 16:48, 31 May 2020 (UTC)

Selective transclusion prevents information/content on multiple pages that cover the exact same topic from diverging over time. Yes, it does make it harder for unfamiliar editors to edit the source, at least initially when they're unfamiliar with the markup (see WP:SELTRANS for a primer). In this particular case, selective transclusions from amphetamine are used to ensure that this article, dextroamphetamine, lisdexamfetamine, and Adderall uniformly cover the same information in relevant sections. Seppi333 (Insert 2¢) 04:22, 17 November 2022 (UTC)

Reference to fraction bound by plasma proteins

1. I just corrected the value for the fraction bound to 20%, according to the already linked source. Maybe they changed the value at some point. At the moment the source is DrugBank; section Protein binding: https://go.drugbank.com/drugs/DB00182#pharmacology. For said parameter the reference on DrugBank is solely this article: https://link.springer.com/article/10.2165/00003088-200443030-00002. Would it not be better if this source was mentioned in the article instead of Drugbank?

2. I also cross-checked said 20% with other publications and it's about right. So I guess there is no point in adding additional sources to prove the same number?

PENDRAGON (talk) 11:23, 13 October 2020 (UTC)

Dopamine neuron should be changed to dopaminergic neuron

On of the image titles says "Pharmacodynamics of amphetamine in a dopamine neuron" there is no such thing as a dopamine neuron, it should be changed to dopaminergic neuron. — Preceding unsigned comment added by Ihazevich (talk • contribs) 16:22, 17 February 2021 (UTC)

Semi-protected edit request on 24 December 2021

The Safety of Stimulant Medication Use in Cardiovascular and Arrhythmia Patients - American College of Cardiology

yo, stimulants are in fact cardio protective. has anyone given careful thought to this? The heart is a muscle. Muscles become stronger the more they work, The faster the heart beats the more oxygen is delivered. Blood circulates faster. these are good things. w/out preexisting heart conditions theres no issue… do marathon runners die prematurely? … i’ve taken these medications for decades - its only Vyvanese that has brought premature aging up - the 80 years before Vyvanese no one conclusively proved stimulants shorten people’s life spans. The truth is probnly that the way Vyvanese is metabolizedin the live by whatever enzynmee is it is in the liver that activates it causes long-term live damage and when your liver is gone - its over. Lastly speaking from personal experience Real Dexedrine or Adderall make my heart beat WAY faste than Vyvanese so that simple fact tells me this is to put it politely, highly questionable and to put it bluntly, bullshit . and if you drive a car on on overdrive but give extra attention to maintainihg it it will last long - its only if you aren’t healthy or dont maintauin your car in the first place that a issuew MAY come up. and people if you don’t know for god’s sake, if your skin doesn’t look good drink more water until you’re drinking 6liters a day. I bet crackheads who drink 6 liters of water a day have great skin! 72.143.21.46 (talk) 07:39, 24 December 2021 (UTC)

 Not done: it's not clear what changes you want to be made. Please mention the specific changes in a "change X to Y" format and provide a reliable source if appropriate. Cannolis (talk) 07:43, 24 December 2021 (UTC)

Policy on chemical data

I am curious about what the policy is for including physicochemical data for pharmaceutical drugs. The box in this page gives the data for amphetamine base racemate, yet this is not a form that is available on the market, legal or illegal. There are of course many different salts and derivatives of the compound with different chemical structures and physical properties. Is it standard to give the base form of amines? How about tertiary amines, which have no stable base form and potentially different counterions? Would it make more sense to include all the common salts? Or perhaps have another page dedicated to it? Kilgore T (talk) 13:31, 26 October 2022 (UTC)

In the US, there are at least two brand names of amphetamine, EVEKEO ODT is the racemic sulfate salt, while DYANAVELXR is a 3.2 to 1 mixture of d- to l-amphetamine and is a mixed salt. I don't think it is practical to list all the avaiable salts, nor enantiomeric mixtures in the physicochemical properties section of the infobox, so I think it is appropiate to limit this section to the parent racemic free base. Tertiary amines are stable compounds that can be isolated. It is the quaternary amine which when isolated, must be complexed with a counter ion. Amphetamine is a primary amine. I would not object if someone wanted to create a seperate data sheet for the racemic sulfate, etc. Boghog (talk) 07:41, 27 October 2022 (UTC)

Semi-protected edit request on 8 April 2023

Má huáng 1015 (talk) 22:25, 8 April 2023 (UTC)

i think it would be better if the image that shows the structure of amphetamine in 2D would be replaced with the image that Wiktionary uses the reason why i think this change should be made is the image from wiktionary shows that there are two enantiomers i do want to make it clear that i don't know a lot about chemistry unfortunately https://en.wiktionary.org/wiki/amphetamine#/media/File:Amphetamine-2D-skeletal.svg

 Not done for now: the image doesn't look line an improvement, though you're welcome to seek consensus for the alteration. M.Bitton (talk) 19:33, 9 April 2023 (UTC)

Removal of lack of neurotoxicity in humans statement due to serious misinterpretation of the sources

Please either remove "There is no evidence that amphetamine is directly neurotoxic in humans" or change to "The neurotoxicity in humans under therapeutic doses is currently not understood" as there is no basis to sustain the current sentence using current citations.

"Amphetamine". United States National Library of Medicine – Toxicology Data Network. Hazardous Substances Data Bank. Archived from the original on 2 October 2017. Retrieved 2 October 2017. Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.

This citation is talking about vascular toxicity in the brain, rather than neurotransmitter toxicity (neurotoxicity), thus can't sustain the above statement.

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. p. 370. ISBN 9780071481274. Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.

This citation is a secondary source with no basis on research.

Throughout my search for alternative sources, I have not found any concrete research into neurotoxic effects in humans rather than lab animals at all. Review of the existing literature links to effects in humans being not understood

Thus I believe that the sentence as it is currently written in the article leads readers to false conclusions that it's safe to take amphetamines in therapeutic doses as there is research with no evidence, rather than that there is no research at all. Ritave (talk) 16:30, 24 April 2023 (UTC)

@Ritave: The Toxnet source does indeed talk about neurovascular damage. It's still a form neurotoxicity. The molecular neuropharmacology textbook is a graduate-level text written by three researchers who read, perform, write, and synthesize research in this field. In fact, one of them is heavily cited throughout this article. In any event, it is a WP:MEDRS-compliant source.

That being said, Amphetamine has been a pharmaceutical drug with an ongoing medical use for 80 years; in spite of the large population size of active medical amphetamine users, researchers have not identified neurotoxicity in the brains of individuals who take amphetamine pharmaceuticals at therapeutic doses and published a paper about it. You can't "prove" a negative finding with the vast majority of statistical hypothesis tests employed in statistical models; that's just not how statistical inference works. Hence, why nobody publishes papers saying "hey, we did all these brain scans and found that amphetamine is not neurotoxic". What you can say is, "we failed to detect evidence of neurotoxicity", but literally no one publishes research papers with a negative result like that because it's not a research finding (seriously, I challenge you to find one); rather, it's a lack of one. If you expect a stronger statement to be made based on more research, you'll be waiting a while because that will never happen. Seppi333 (Insert 2¢) 04:50, 7 May 2023 (UTC)

Thank you for the explanation, it helped me understand a different view.

Regarding the first citation, I'd say using data showing no dangers in a subset of a category by extending it to a whole category is misleading. Especially when the main mechanism of action of the drug is based on a nervous system rather than the vascular system.

I understand that Amphetamine was not found to be neurotoxic and I don't expect research stating negative result to exist. I tried to find one before asking for a change.

The sentence I'm asking to change is making deductions rather than inductions from the data to a general audience, creating a sense of security about a topic. That sense of security might be well based from unwritten experience of doctors over the world, but as a layman, I could not find more data outside of this single book that would either confirm or deny such statement.

Rather than strengthening the statement on more data, I'm asking to relax the statement to a more ambiguous one, more in line of the intent of "it should be safe to administer based on previous experience" rather than "it's safe to administer and here's proof of such". Ritave (talk) 20:39, 21 May 2023 (UTC)

Amine

Shouldn’t “amine”, located in the very first paragraph, be transformed into a link?

Is there a reason it hasn’t? HockeyCowboy (talk) 09:31, 28 April 2023 (UTC)

I did. Hope that’s ok. HockeyCowboy (talk) 05:54, 30 April 2023 (UTC)