Talk:Dopamine reuptake inhibitor

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Untitled

Sounds ok.

Daevatgl 20:35, Jun 16, 2004 (UTC)

May 6 2005 edits The Biochemical Basis of Neuropharmacolgy Oxford Press 1996 Chapter 9 Dopamine--McDogm 17:21, 6 May 2005 (UTC)

Should add Adderall in here -- I would but couldnt figure out the proper medical name for it or where it fits in terms of dopamine release.

Binding ligands?

Isn't it the case that most phenethylamine DARIs inhibit by attaching as if they were the regular transporters, and others like the cocaine tropane-types attach or bind as a ligand to the transporter in an entirely different way? It is odd that such a tropane type ligand, if I'm not mistaken, attaches with a higher affinity? 71.34.103.210 (talk) 00:45, 19 April 2009 (UTC)

( I'm assuming that by "regular transporters" you meant "regular, to-be-transported substrate" or "endogenous substrate". ) In general, the 2D structure of a drug does not reliably predict its activity ; The fact that some DRIs have a phenethylamine substructure does not mean much.

The existence of multiple DAT sites and multiple DAT conformations is the subject of on-going research, and AFAIK, it's inconclusive. You can look into :

• PCP site 2, an hypothetical "monoamine transporter negative allosteric modulator site". ( “PCP site 1” would just be a complicated name for NMDAR’s ion channel. )
• Difluoropine, claimed to fold DAT in an inward-facing conformation, meaning it inhibits the reuptake of dopamine but also inhibits its transporter-mediated release.
• Similarly, SoRI-9804 is also claimed to inhibit the reuptake of dopamine while also inhibiting its transporter-mediated release.
• SoRI-20041, claimed to inhibit dopamine reuptake without blocking d-amphetamine mediated release (transport reversal).

77.146.231.162 (talk) 17:15, 16 March 2023 (UTC)

Two Errors corrected 9-7-09

I've corrected the following two errors:

• removed benzatropine from the list of DRIs. Benzatropine is an anticholinergic, it has nothing to do with dopamine and dopamine receptors. Its use in Parkison's and other movement disorders has to do with the balance of activity between cholinergic and dopaminergic components of the deep brain movement centers, but it has no effect on dopamine itself.
• added cocaine to the pharmaceutical agents; in the USA it is schedule II, not schedule I, and has important medical uses in ENT/OHNS surgery. —Preceding unsigned comment added by 208.80.67.18 (talk) 17:11, 6 September 2009 (UTC)

Benzatropine/benztropine is a DRI, hence why I put it on the list: Source. And while cocaine is a pharmaceutical, it's primarily a street drug and its medical use is almost unheard of, so I think the illicit category would be more appropriate. Not to mention its DRI actions aren't actually related to its clinical use either. el3ctr0nika (Talk | Contribs) 09:42, 24 January 2010 (UTC)

Dubious

I tagged the link to physical dependence as dubious. To my knowledge, straight DRIs such as methylphenidate don't cause a lot of "physical dependence". This is partly a language issue: These drugs do cause homeostatic changes in the brain, but philosophy of the mind notwithstanding, I think that that's not usually what is meant by "physical dependence". In my book, "physical dependence" means that there are serious peripheral symptoms upon discontinuation. Suboptimal Username (talk) 17:15, 10 June 2010 (UTC)

There are withdrawal symptoms upon discontinuation, look at cocaine - huge withdrawal symptoms. Even methylphenidate when used at a high enough dose will give withdrawal symptoms --Axxaer (talk) 04:17, 27 September 2010 (UTC)

Cocaine is totally different though, according to the wiki page it is a Serotonin, Norepinephrine and Dopamine reuptake inhibitor. Methylphenidate as well is not selectively a dopamine reuptake inhibitor. I don't really get why you make the link between those two and DRIs Robinsona (talk) 20:47, 11 December 2010 (UTC)

Dopamine reuptake inhibitor that acts just toward the DAT class which dopamine releasing agents can select out of one of either

e.g. dextro- & levo- methamphetamine. Could there be a drug similar to cocaine for instance, that only preforms the function of the former mentioned dextro- (alone) or levo- (alone) by only inhibiting reuptake on those sort of transporters potentially at all? Nagelfar (talk) 05:47, 8 July 2010 (UTC)

- Levo- and Dextro- are (outdated) terms that refer to a compound's stereochemistry (its enantiomers), not its binding sites.

- What you’re referring to as a “DAT class“ is likely just NET.

- Levo-amphetamine and Levo-methamphetamine are selective norepinephrine releasing agents, meaning they have negligible effects (“no effects”) on dopamine transmission at therapeutically relevant doses. The reuptake inhibitor equivalent would therefore be a selective norepinephrine reuptake inhibitor. 77.146.231.162 (talk) 15:24, 16 March 2023 (UTC)

Roosevelt University PSYC 336 Project

Basic Outline

List of DRI’s and Intro: will simply be edited according to our research findings, and addition DRI’s not listed will be added, and the current list verified.

Process

This section will contain information about the biological processes induced by dopamine reuptake inhibitors. The process within the synapses will be covered, alone with any side effects, either long term or short term, as well as any effects caused by dopamine increase.

History

This section will cover the history of the discovery and use of dopamine reuptake inhibitors. The development over the last half century of the targeting of transporters as a means of concentrating levels of neurotransmitters within the synapse will be discussed, as well as a general history of the drugs and their discoverers.

Possible affects on cognition

This section will focus on the affects that DRI can have on emotion, as well as the possible side affects of DRI's. Another subject that this section will talk about is the controversy behind DRI's in drugs. This will touch on usage and abuse of DRI's. This section will also touch on the short term affects and the long term affects of DRI's.

Dopamine Reuptake Inhibitors and Depression — Preceding unsigned comment added by Nszynal-ru (talk • contribs) 17:50, 12 November 2012 (UTC)

— Preceding daniadams9121 comment added by Narmstrong484 (talk • contribs) 18:49, 9 October 2012 (UTC)

Instructor's comments

• Group, I like your outline, but I don't see how you're going to be able to write this with primary sources as you've listed. Look for secondary sources such as books or review articles. Use a medically based database such as PubMed. I will also email this group a chapter on dopamine. It's a bit old, but it might be lead to other sources.

Neuropsychprof (talk) 22:00, 10 October 2012 (UTC)

Schandler91 Comments

Well I see that we all know that you need more sources I think its a good start though just a little more information in certain sections and more sources and I think this will be a good article, Good luck — Preceding unsigned comment added by Schandler91 (talk • contribs) 17:47, 30 October 2012 (UTC)

Smallman12q comments

• Needs more sourcing.
• There is a lot of research in this. Discuss current/future research.
• Add similar sections to those in Selective serotonin reuptake inhibitor.

This is a good start...but needs a lot of expansion/sourcing.Smallman12q (talk) 22:38, 27 October 2012 (UTC)

Comments

It looks like there needs to be more sources that are actually contained within the article rather than just floating at the top. More sections should also be added to go into details about subjects raised in the introduction. I would agree with smallman12 that the article needs to be expanded and more effort needs to be put into finding sources.

Pmisner2009 (talk) 16:39, 28 October 2012 (UTC)

I agree that maybe more sources would help generate a better informative article. I think what you have so far is good but maybe you could expand upon certain parts as in the dopaminergic pathway and get into more detail. R.EEGbrittry (talk) 19:51, 29 October 2012 (UTC)

Comments from rorystewart

• This is a good start, but I do feel that expansion will be needed. Look to expand on how synaptic cell signalling works and how active sites are affected.
• Your list of inhibitors are great, although it is assembled strangely. I would remove the bullet points without any information provided on them (there are a few in the list).
• More references are needed. This information is not common knowledge, so I would work on being sure you add the needed citations to your page.
• What research is being done working with DRI's? this would be an interesting section to add to your page.

--Rorystewart (talk) 18:32, 30 October 2012 (UTC)

Comments from Keilana

Hi everybody! I just got a message from Prof. Lu asking if I could take a look at everybody's work, and I've got a few suggestions to help make your article even better. I'm going to organize them in a bullet pointed list just for your ease of use; if you have any questions or need some help, you can either ask here (I've watchlisted this talk page) or on my talk page. I'm happy to help with anything! =]

• You've got two inline citations at the very top of the article, before the text. Inline citations always go after the sentence(s) they cite so that the reader knows where the information they're reading has come from.
• That said, the first, second, and fourth paragraphs require inline citations to ensure verifiability. I'm assuming that information came from those first two citations, so it shouldn't be too hard to move them to where they should go.
• In the last paragraph, I think you meant to say "ginkgo biloba" - when I hear "ginkgo balboa" I think of Rocky's long-lost sibling. But I could be wrong! Just wanted to make sure.
• Instead of having a list of the different DRIs, I think you should make paragraphs. You could have a section each for "selective dopamine reuptake inhibitors", "DRIs with activity at other sites", "Other DRIs", "Natural dopaminergetics", and "Dopamine controlling drugs". That would be really helpful to the reader.
• Though I think the information in the notes at the bottom is useful, it needs to be incorporated better. Either you could make a section/paragraph out of that information or you could use <ref> tags to create a footnote. If you want help making a footnote, I'd be happy to help. :)

All the best, Keilana|^{Parlez ici} 06:09, 31 October 2012 (UTC)

Instructor's feedback

Group, you have added some good info on a tough topic. I'm going to email this group some readings that may help. Remember to refer to the selective serotonine reuptake inhibitor page for the type of info to add to your article. Note this article is dopamine reuptake inhibitor, not specific dopamine reuptake inhibitor. This means that you can include info on agents that inhibit both dopamine & norepinephrine. It will also be good to compare and contrast dopamine, norepinephrine and serotonine reupake inhibitors with the aim of clarifying specific effects of dopamine reuptake inhibitors. Note dopamine should not be capitalized unless it's the first word in a sentence. Keep up the good work! Neuropsychprof (talk) 08:12, 5 November 2012 (UTC)

Changes based on Feedback and Feedback not addressed

Thanks to everyone who gave us suggestions to improve our article! While all of the suggestions were very helpful here is what we focused on:

• Grammatical errors, rewording of sentences out of essay format and more into wiki format.
• Add more wiki-links and fix citations.
• Work to improve organization of the article.
• Include expanding discussion of Bupropion and MDMA, giving both of these their own sections (and discussing some of the current research on them.)
• Adding a Society and Culture section and starting on a history topic (As similar to Serotonin Reuptake Inhibitor article)
• Expanding the introduction about the subject.
• Incorporating the articles Dr. Lu sent us into our article on DRI's (added secondary sources.)
• Fixing the list of DRI's to make it a paragraph instead of list form, as suggested by Keilana.

Unfortunately, we were not able to get to everyone's feedback. Here are a few and the reasons why:

• Finding Future research on this subject was quite a challenge. The articles we found did not have a section on future research on the subject and it was incredibly challenging to find anything relevant on the internet about our subject that could be reliable.
• Current research on the subject is also hard to find on the broad subject of DRI's but we found some good research on MDMA's and Bupropion.
• We did not compare and contrast dopamine, norepinephrine and serotonine reuptake inhibitors in our article due to lack of research on the subject.

Thanks to everyone for all your feedback and suggestions, it was very helpful! Best wishes. Daniadams9121 (talk) 19:24, 13 November 2012 (UTC)

Why does this article have a section on MDMA?

I notice that one of the main sections of this article is on MDMA, and I find this peculiar. Firstly, because MDMA is primarily a releasing agent (rather than a reuptake inhibitor), and secondly because MDMA mainly acts on the serotonin system, although its effects on noradrenaline and dopamine are also important. There are much better examples of dopamine reuptake inhibitors than MDMA, such as methylphenidate, ethylphenidate, MDPV, pyrovalerone, and bupropion. If there is not a good reason to have this section, then I suggest that it should be removed. Woood (talk) 08:24, 3 December 2012 (UTC)

I agree with the above, MDMA is a mixed action dopamine reuptake inhibitor and releasing agent. And even then is not a very potent one compared to its action at SERT and it's true magic in reversing, or breaking VMAT-2. In fact because of its status as a Schedule I we really don't know if the dopamine release is primary to its structure or if it's secondary to serotinergic activity. As an MDMA user who has also used amphetamine, methylphenidate and bupropion medicinally it seems likely to me that the after effects of MDMA on me (getting sleepy and wanting to go to bed) are not characteristic of a strongly, primary dopaminergic compound with such a long half-life. — Preceding unsigned comment added by 208.102.254.241 (talk) 22:36, 20 December 2012 (UTC)

Potential inaccuracies and/or false assumptions

I'm concerned at the ambiguity of the definition. It is my understanding that dopamine reuptake inhibitors must have a very low affinity for dopamine and norepinephrine, drugs with these characteristics are classified as SDRI and NDRI's respectively. Wiki pages exist for them.

Additionally, the introduction is confusing, contradictory, and informal.

"Many physicians disagree with the information noted above that is biased against the use of DRIs and stimulants because of some potential of abuse."

This is a perfect example, I have absolutely no idea what it is meant to mean.

"To date, we know of no abuse of drugs such as Bupropion."

Incorrect, publicly available literature is found in the first link when searching google for "Bupropion abuse potential."

" Contrary to the writers opinion above..."

I doubt its necessary to explain why this paragraph needs to be edited. The bias displayed in it is enough for me to have made my first addition to a Wikipedia page.

"...the only norepinephrine-dopamine reuptake inhibitor (NDRI) approved by the Food and Drug Administration."

Methylphenidate?

Regardless, I believe I've made my point, This article is probably not worth salvaging, perhaps it should be re-written from scratch?

124.183.98.85 (talk) 17:17, 7 July 2013 (UTC)

Assessment comment

The comment(s) below were originally left at Talk:Dopamine reuptake inhibitor/Comments, and are posted here for posterity. Following several discussions in past years, these subpages are now deprecated. The comments may be irrelevant or outdated; if so, please feel free to remove this section.

Changed rating to "mid" for consistency within MCB project. This article needs an explanation of the pharmaceutical/biological effect of these inhibitors in simple terms; it's very technical right now. - tameeria 20:10, 22 February 2007 (UTC)

Last edited at 20:10, 22 February 2007 (UTC). Substituted at 13:40, 29 April 2016 (UTC)

Modafinil/armodafinil as a selective DRI

All the information I've read indicates that modafinil (or at least R-modafinil; I've not seen much written about L-modafinil) acts as a reuptake inhibitor which is selective for DAT (unlike, say, cocaine, which significantly inhibits DAT, NET and SERT, or methyl/ethylphenidate, which significantly inhibits both DAT and NET). Ignoring the difference in half-life, (R-)/modafinil's binding profile seems to be more similar to amineptine's than anything else. IMHO, this ought to be reflected in this article. I'm aware that the armodafinil article claims that it has "effects and feelings consistent with methylphenidate", but I'm skeptical of that claim; it appears to be based on a single study, whereas many other studies have found that both in vitro and in vivo the drug binds nearly solely to the DAT, and even Wikipedia's own modafinil article states that "it was found to significantly affect only the dopamine transporter". --Mojace (talk) 13:21, 25 April 2017 (UTC)

Modafinil is selective for DAT as opposed to NAT and SERT, yes, but modafinil is also claimed to be an agonist at alpha1B-adrenoceptors. -- Mentropane (talk) 20:47, 27 November 2019 (UTC)

Fluorenol

It is my understanding that it is the fluorenol-derivative of modafinil that is a weak DAT-inhibitor, and not fluorenol itself.

-- Mentropane (talk) 20:52, 27 November 2019 (UTC)

It appears that it is fluorenol itself after all; see the Talk page for Fluorenol. -- Mentropane (talk) 15:25, 28 November 2019 (UTC)

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