Talk:NMDA receptor antagonist

message: Not all NMDA receptor antagonists are anaesthetics, as the opening line of the article suggests. Look at memantine or l-theanine. I do acknowledge, however, that the most talked-about NMDA antagonists are dissociative anaesthetics as well.  —Preceding unsigned comment added by 99.248.230.140 (talk) 01:22, 25 February 2008 (UTC)
thread_title: Glaring Error!

message: I see you put this in there: "However, many researchers have lost hope for development of a neuroprotective NMDAR blocker, since no clinical trials using the drugs for stroke or TBI have been successful." The opinion you cite there isn't quite as decisive in saying "researchers have lost hope," and the way you present it rules out the possibilites of combining NMDAR antagonists with other drugs (like GABA-A agonists) to protect against NAN. Take a look:  , 
 ,  . Jolb 22:59, 17 January 2007 (UTC)
replies: text: Well, I think a lot of researchers have given up on NMDAR blockers and a lot haven't. Certainly not everyone has given up.  So I don't have a problem with changing the wording, go ahead.  I think the major disappointments with the drug trials mostly occurred in the late 90's and the early part of this decade, so the paper from 1991 might be too optimistic.  I just added a lot about said disappointments, let me know here if there's any problem with the material.  delldot | talk 02:49, 18 January 2007 (UTC)
replies: text: Actually, now that I think about it, this may be more the case in my area of specialty, traumatic brain injury.  Obviously no one's giving up on memantine for the treatment of Alzheimer's, since it was just FDA approved for the purpose.  So you're probably right that it needs changing: edit at will.  delldot | talk 02:58, 18 January 2007 (UTC)
thread_title: Lost hope?

message: I vaguely recall from somewhere in the manual of style it suggesting that you don't put links in the bold part in the lead.  I'll look around and see if I can dig it up.  If I can find it, would it be OK to move the links slightly further down? delldot | talk 02:49, 18 January 2007 (UTC)
replies: text: Ah ha, here it is.  Wikipedia:Manual of Style (links)#Internal links: "As a general rule, do not put links in the title; however, this may be acceptable with complex titles or verbose leads, such as those concerning multiple concepts."  This case might qualify as a complex title, so I guess it's fine either way.  I have a vague preference for unlinking the title, any objection?  delldot | talk 02:56, 18 January 2007 (UTC)
thread_title: Links in lead

message: Wow, thanks for that graphic, delldot. You're much more of an expert than me, so I have a question about this article: From what was written in NMDA Receptor, I saw (most) of the list of NMDA Receptor Antagonists, including the part about "non-competitive channel blocker." According to your graphic, however, channel blockers don't go with "non-competitive," they go with "uncompetitive." I'll do some research on this and try and find out myself, but maybe you know. Jolb 22:05, 17 January 2007 (UTC)
replies: text: Thanks, glad you like it!  I think different researchers classify them differently.  With most enzymes, it's either competitive or non-competitive inhibition, so probably most researchers look at it as "competitive" and "everything that's not competitive".  When you get something with a channel, it's useful to make a further classification.  But they're still, of course, not competitive, so some researchers still probably look at it that way.  This is my guess.  I've seen a number of different papers refer to uncompetitive blockade, I can look for them and hopefully stick them in.  I noticed memantine listed as non competitive and listed it as uncompetitive.  Peace, delldot | talk 22:32, 17 January 2007 (UTC)
thread_title: Non-competitive or uncompetitive?

message: I'd suggest moving this page to NMDA receptor antagonist since the naming conventions recommends sentence type capitalization (Capitalize the first letter and not the others unless there's a proper noun) and singular nouns except where you usually see it in the plural (e.g. French fried potatoes).  Any objections or discussion?  delldot | talk 22:32, 17 January 2007 (UTC)
thread_title: Move? (from the incorrectly capitalized article)

message: I'm going to put a  template on the article, so an admin will come along, momentarily delete the article, and restore it with the history of NMDA Receptor Antagonists merged into this article's history.  That way, jolb still gets credit under the GFDL for creating the article, etc.  You can read more at WP:MOVE.  delldot | talk 16:27, 18 January 2007 (UTC)
replies: text: OK, I finished the history merge, including the history for both the talk pages. Cool Hand Luke 00:40, 20 January 2007 (UTC)
replies: text: Thanks CHL!  delldot | talk 04:12, 20 January 2007 (UTC)
thread_title: Move

message: I think that this article is a model article. It's well written, well referenced, has a very appropriate diagram, and not too long or short. Thank you, delldot! We should try to get it rated by an admin, as I'm sure it would get an A. Jolb 13:48, 13 February 2007 (UTC)
replies: text: Most of the credit goes to you, of course.  I suggest that we add some more information and then submit it for peer review, especially since neither of us is an expert.  That way we can be sure to have all our facts straight when we go for GA later.  I'm willing to work on adding info in the upcoming week.  Thanks again for all your great work, Jolb.  delldot | talk 14:36, 13 February 2007 (UTC)
thread_title:  This is a beautiful article 

message: Hi there, I didn't think this was quite at GA level yet. What is here is good, but the article is not comprehensive.
Positive aspects of article
Well referenced
Good, clear diagram
Negative aspects of article
Too short and fails to explain subject completely.
Suggestions - Need more sections and more background. Most importantly, a section on the physiological/biochemical effects of these drugs. Also a history section outlining the development of the field and also uses of these drugs in folk medicine/natural product psychoactive drugs, a section on modern psychoactive drugs and a section on clinical trials. 
The fragment on Olney's lesions doesn't belong in the introduction and needs to go with the rest of the material on side effects.
Hope this feedback helps. TimVickers 18:36, 16 February 2007 (UTC)
thread_title: GA review

message: I'll finish this this weekend, but here's some opening thoughts.
*At some point during the article, NMDA needs a wikilink.
:Done.
*Don't wikilink words in the bolded title of the article.
:Done.
*"dissociative anesthesia" should not include the quotation marks in the wikilink.
:Done.
*How are they created?
*Go into more detail about the recreational use of these drugs. For example, how has the usage changed over the years, particularly in comparison to other anesthetics?
*Tell us something about the history of these ANTs. When where they first discovered? How did they become common drugs?
*The diagram is great. However, you have to assume that the reader won't look at it. Therefore, you need to write about the mechanisms of the receptors in prose in much more detail than in the current Mechanism section.
:Could you be more specific?
*Are they metabolized in any common way?
:Done.
*Remove the wikilink to Olney's LEsions in the excitotoxicity section.
:Done.
*Tell us about tolerance/sensitization of the drugs. Teemu08 21:51, 29 June 2007 (UTC)
replies: text: Done. Thanks for your help! Jolb 19:18, 30 June 2007 (UTC)
replies: text: I made an attempt. Is that satisfactory? Jolb 15:44, 1 July 2007 (UTC)
thread_title: Partial GA review

message: Does anyone know of any references for this? I'd like to know the dosage e.g. mg/kg that is required for ethanol to act as an NMDA antagonist.  —Preceding unsigned comment added by Darobian (talk
• contribs) 14:00, 15 December 2007 (UTC)
thread_title: Ethanol as an uncompetitive antagonist

message: It has been shown in human studies that nicotine potentiates nmda receptor antagonist neurotoxicity, this is due to binding at the  nicotinic cholinergic sites. As nicotinic antagonists prevent NAN.  — Preceding unsigned comment added by RewB (talk • contribs) 14:48, 25 August 2016 (UTC)
thread_title: Nicotine potentiated NAN

message: I have a 2004 paper from the Journal of Pharmacology and Experimental Therapeutics (R Pechnick, R Poland) that cites three different studies over a seven year period to this effect. It is definitely relevant as well, seeing as noncompetitive NMDA antagonists specifically block the allosteric control site of the receptor, rather than the active glutamate or glycine sites. I will attempt to complete my bibliography on these references and correct this later this evening. arquin (talk) 13:36, 5 July 2008 (UTC)
thread_title: Dextromethorphan is noncompetitive, not uncompetitive

message: Would Hodgkinsine fall under the 'Uncompetitive channel blockers', 'Noncompetitive antagonists', 'Glycine antagonists' or 'Competitive antagonists'? Nagelfar (talk) 05:37, 31 October 2008 (UTC)
thread_title:  Hodgkinsine 

message: In the clause about schizophrenia's link to NMDA hypofunction, there is an article used as reference: . That was one of the small studies that eventually led to a multicenter human study that did not show improvement from glycine cite modulation. And anyway the reference covers little of the NMDA-schiz. relation theme, so I propose to put instead link to Bita Moghaddam's "Glutamate Hypothesis of Schizophrenia" (at Schizophrenia Research Forum.) --CopperKettle (talk) 22:34, 6 December 2008 (UTC)
thread_title:  Glycine study as a reference - results doubtful 

message: One of the isomers of methadone has NMDA receptor antagonism (the other is a mu/kappa agonist), and it is probably contributatory to the analgesic effect in some types of chronic pain.  Of course, the mu/kappa agonism are likely the major factor.  —Preceding unsigned comment added by 24.63.197.74 (talk) 17:13, 2 April 2009 (UTC)
thread_title:  Need to add methadone 

message: If a distintion between uncompetitive and non-competitive needs to be made these chemicals are in the wrong categories.
Memantine - binds to the Mg site therefore would be considered non-competitive by the current standards on the page.
MK-801 - binds to the PCP site therefore would be considered uncompetitive.
75.204.244.160 (talk) 11:08, 16 April 2009 (UTC)
thread_title:  Uncompetitive / Non-competitive Errors 

message: On the Magnesium Salicylate page it says that is also "an NMDA receptor antagonist very mild in action". Is Magnesium Salicylate an NMDA receptor antagonist?  Kildwyke (talk) 17:05, 16 June 2010 (UTC)
thread_title:  Magnesium Salicylate 

message: The Neurotoxicity header contains the sentence "Other drugs acting on various neurotransmitter systems known to inhibit NMDA antagonist neurotoxicity include: anticholinergics, diazepam, barbiturates,[22] ethanol,[23] 5-HT2A serotonin agonists,[24] and muscimol.[25]"  This sentence contains an ambiguous construction whereby it is unclear from context, to a nonexpert like myself, whether it is "other drugs" or "neurotransmitter systems" that are "known to inhibit NMDA antagonist neurotoxicity." Either reading makes grammatical sense, and I for one don't know whether, for instance, ethanol (no matter how much it might promote plain-vanilla neurotoxicity) does or does not inhibit (specifically) NMDA antagonist neurotoxicity, or whether it does or does not act on neurotransmitter systems that do so.  I know absolutely nothing about pharmacology, so no way am I going to touch that sentence myself, but the two available readings are essentially opposite so should be fixed.KASchmidt (talk) 21:12, 1 February 2011 (UTC)
thread_title:  Ambiguity in Neurotoxicity section. 

message: Why is ketamine listed as a non-competative allosteric modulator, rather than an uncompetative channel blocker? It clearly shares its chemical structure with PCP, tiletamine etc, which all bind to the PCP site within the NMDA receptor. The ref given (no 43) is very old - 1985 - and though it refers to ketamine as non-competative, I would suggest that this is due to confusion between "non-competative" and "uncompetative" as mentioned in the discussion below. I find nothing in any of the references given to suggest ketamine is anything but an open channel blocker, binding to the PCP site.
Bunney el al "Schizophrenia and Glutamate: An Update" clearly states this - http://www.acnp.org/g4/GN401000116/Default.htm
Tryptych0 (talk) 20:08, 7 November 2011 (UTC)
replies: text: This is a very good question, but I think it should be asked the other way round. As far as I understand it, the allosteric binding site is the so-called "PCP binding site". So if I am not mistaken, most of the compounds (at least all arylcyclohexylamines, but probably even much more than those) that are listed now as uncompetitive channel blockers are actually non-competitive antagonists. --Diogenes2000 (talk) 00:20, 16 November 2014 (UTC)
thread_title:  Ketamine 

message: I am removing the following sentences from the introduction, as they seem self-contradictory and are inconsistent with what is laid out in the Neurotoxicity section:
There is evidence that NMDA receptor antagonists can cause a certain type of neurotoxicity or brain damage referred to as Olney's lesions in rodents, although such damage has never been conclusively observed in both adult primates or humans. Recent research conducted on primates suggests that, while very consistent and long-term ketamine use may be neurotoxic, acute use is not.
The Neurotoxicity section is not particularly well written, but this back-and-forth in the beginning of the article is useless and redundant. I recommend a more concise phrasing, if it must be in the introduction at all.
From the Neurotoxicity section:
Although NMDA antagonists were once thought to reliably cause neurotoxicity in humans in the form of Olney's lesions, recent research suggests otherwise.
From the sources it looks like the jury is still out on Olney's lesions, but at least there is some new research and, in light of this, it should be concisely reexamined in the Neurotoxicity section.
68.197.59.144 (talk) 08:26, 7 June 2017 (UTC)
replies: text: Cool, thanks for improving the article! This is a classic WP problem since articles are so often cobbled together by different people at different times. I don't know about that bot but it may just have reverted you because you were not logged in and removed material, a common MO of vandals. It's been forever since I edited this or knew anything about it but LMK if I can be of any help. delldot ∇. 23:33, 26 June 2017 (UTC)
thread_title:  Inconsistent introduction