Talk:Venlafaxine

Memory Loss

In previous versions of this page, there was mention (sourced) about side effects such as memory loss. The numbers found in the study seem quite profound in regards to memory loss. Why does no such information exist anywhere on the page anymore?

See this diff where it was removed: https://en.wikipedia.org/w/index.php?title=Venlafaxine&diff=next&oldid=580354405

Originally sourced: Tolerability of High-Dose Venlafaxine in Depressed Patients http://jop.sagepub.com/content/18/2/200 — Preceding unsigned comment added by 207.195.114.48 (talk) 14:07, 10 February 2016 (UTC)

Potential errors

First paragraph of the article In children and adolescents, venlafaxine (like other anti-depressants) has a potential to increase suicidal thoughts, attempts and events of self-harm.

Im sure this is meant to read decrease suicidal thoughts? —Preceding unsigned comment added by Fmountford (talk • contribs) 10:45, 30 March 2010 (UTC)

No, actually, there is a small risk of increased suicidal thoughts in some patients, but it is more likely more patients will have fewer suicidal thoughts. I don't have the citation, but one study showed that after the FDA forced most antidepressants to have the "black box warning", the overall number of prescriptions written decreased, and overall suicide rates increased, showing that overall, antidepressants reduce suicide risk. MeekMark (talk) 16:46, 6 May 2010 (UTC)

Should that be moved to a different section of the page? Granted, it does have a grain of truth, but the way it comes off, it sounds like anti-medication propaganda. --174.30.2.239 (talk) 00:28, 11 February 2011 (UTC)

I have removed this sentence because anyone looking at the TOC will immediately notice Suicide as the first thing under Side Effects. Besides, this problem is not nearly as common as the media presents it: the difference didn't even reach statistical significance for any single drug, so they had to do a meta-analysis of many antidepressants to be able to report an increase. If you have a good reason to revert, please notify me and post here. Atxd00d (talk) 03:51, 16 February 2011 (UTC)

Discontinuation syndrome versus withdrawal

I re-named the section which was labeled "Discontinuation syndrome" to identify it as "withdrawal." "Discontinuation syndrome" is a Wyeth-created term. I have some concerns that this article has been and continues to be a re-stating of Wyeth provided information only, and without an anlysis of all aspects. While I fully realize that Wikipedia is to maintain a neutral tone, I strongly believe that this terminology ("discontinuation syndrome") is and of itself negates any neutral tone to this article whatsoever.Also use it for man-power.

error regarding pulmonary hypertension

In the section entitled "Heart Disease and Hypertension", a risk for "persistent pulmonary hypertension (PPHN)" is listed as a potential side-effect of this med. PPHN actually stands for "persistent pulmonary hypertension of the newborn". I believe the potential side-effect intended here is for "primary pulmonary hypertension" (PPH), as newborns are unlikely to be exposed to this drug. Also, 4 bpm increase in heart rate is listed as a side-effect under this heading, and is the only cardiac symptom listed under that heading, so I believe "heart disease" is not an appropriate heading here unless additional cardiac risk factors are added to the section. A more appropriate title heading would be for example, "Cardiopulmonary Effects and Hypertension." The section also lacks sources.

If no one objects to these changes in the next few days, I'll make these edits. O'Hush (talk) 02:30, 7 July 2010 (UTC)

Suggested edits applied. Michael.j.lacey (talk) 10:33, 26 March 2013 (UTC)

Side effects

If the source for the rare side effects is the same as for the side effects in the section above, I've checked it out and these were not all controlled studies. Several studies are lumped together in the pre-assessment phase. It's possible these side effects may not have all been due to Effexor. —Preceding unsigned comment added by 205.250.242.207 (talk) 04:15, 8 April 2011 (UTC)

I have now corrected this problem. 205.250.242.207 (talk) 19:11, 9 April 2011 (UTC)

Please explain the sentence: "the remission rate was significantly lower for venlafaxine"

What you wrote re: "the remission rate was significantly lower for venlafaxine" under the subject of "Depression" makes no sense, in comparing it to Wellbutrin. Everything in the surrounding sentences is implying that Effexor is more effective than Wellbutrin, but "remission rate" means the patient is relieved of all symptoms of depression. Please explain.

References

--Pookerella (talk) 19:01, 10 April 2011 (UTC)

Venlafaxine - Is it a Opioid or not?

You can find in the article first it isn't and later it is one.

"Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. These findings suggest venlafaxine's seemingly superior efficacy in severe depression.[61]"

61 - http://www.opioids.com/depression/antidepressants.html

What is right? —Preceding unsigned comment added by 93.181.30.189 (talk) 08:08, 23 May 2011 (UTC)

These are two absolutely different facts about the pharmacokinetics (What is right?):

"In vitro studies revealed venlafaxine has virtually no affinity for opiate, ... receptors. ...[14]"

and

"Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. These findings suggest venlafaxine's seemingly superior efficacy in severe depression.[61]"

Has it interaction with opioid receptors like I think or hasn't it? That`s the question here. —Preceding unsigned comment added by 93.181.30.189 (talk) 19:05, 22 May 2011 (UTC)

Serious problem with the side effect information

I have a problem with this article. The information about Common side effects and frequency of those side effects occurring isn't for standard dosages, it's for dosages equal to or greater than the highest recommended dose of the product. ( http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15260908-31 ) This information is therefore grossly misleading.Webgrunt (talk) 14:12, 9 February 2012 (UTC)

Added discussion of the role of noradrenaline and of discontinuation syndrome resulting from deprivation of neurotransmitters

Very tentative cf my reading of the literature, it would appear to be a usefully up-to-date addition, but comments and discussion invited Michael.j.lacey (talk) 10:24, 26 March 2013 (UTC)

Error in the "depression" section

"In a double-blind study, patients who did not respond to an SSRI were switched to venlafaxine or citalopram. Similar improvement was observed in both groups" this sentence is misleading as citalopram is an SSRI.

The article it is sourced from states "This study was designed to test the hypothesis that, after treatment failure with an SSRI, switching to venlafaxine extended release (ER) would offer advantages over switching to another SSRI, citalopram" and is therefore being misquoted. — Preceding unsigned comment added by Workforidlehands (talk • contribs) 16:00, 28 April 2013 (UTC)

Discontinuation syndrome - first sentence

"In vitro studies revealed venlafaxine has virtually no affinity for opiate, benzodiazepine, or N-methyl-D-aspartic acid (NMDA) receptors. It has no significant CNS stimulant activity in rodents. In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability." - while interesting, these three sentences don't seem to connect in any way with the rest of the section. They just seem odd. Why are they there? Litawor (talk) 18:31, 10 July 2013 (UTC)

Weight Loss or Weight Gain?

This site (http://www.rxlist.com/effexor-side-effects-drug-center.htm) and many others list weight gain as a side effect (on this one, a common side effect), but don't mention weight loss. However, the article mentions weight loss, but not weight gain. Perhaps both could be mentioned?

References

199.223.21.100 (talk) 17:03, 7 March 2014 (UTC) 199.223.21.100 (talk) 17:00, 7 March 2014 (UTC)

Specific negative results interpreted as general positive results, a dubius conjecture, false assumptions.

"Some open-label and three double-blind studies have suggested the efficacy of venlafaxine in the treatment of attention deficit-hyperactivity disorder (ADHD).."

I think the cited studies find that venlafaxine is no more effective than placebo in the treatment of adults with ADHD. Moreover, the abstract of the first article is very vague and basically incoherent, and discloses a bias toward patients belonging to a "substance misuse population". The studies comparing venlafaxine to stimulant medications focus exclusively on children, and measure a positive response to treatment based on evaluation by parents and teachers, not scientists.

There is one (radical?) reference conjecturing that high doses of venlafaxine act as a narcotic. The claims that venlafaxine acts as a sedative or a stimulant are similarly dubious. This article's (assumptions?) that these are common experiences of people who take the drug are quite contrary to reality.

References

Nafindix (talk) 14:24, 16 May 2014 (UTC)

SNRI/SSNRI?

SNRI - selective norepinephrine reuptake inhibitor SSNRI - selective serotonine-norepinephrine reuptake inhibitor — Preceding unsigned comment added by Gladissk (talk • contribs) 14:06, 7 November 2015 (UTC)

Discontinuation

User:128.231.234.33 you have made the following edits:

• diff at 06:11, 6 March 2017 via IP 2601:14a:4500:530:60fd:ea72:19e1:6ccd
• diff at 13:18, 6 March 2017 via IP 2601:14a:4500:530:60fd:ea72:19e1:6ccd
• diff at 18:21, 6 March 2017 via IP 2607:f220:415:611::ab
• diff at 16:19, 14 March 2017 via IP 2601:14a:4500:530:3d89:c6a4:6554:4181
• diff at 13:41, 16 March 2017 via IP 128.231.234.33
• here, diff at 13:51, 16 March 2017 via IP 128.231.234.33 you finally provided 2 refs; both misformatted. The two refs are PMID 9396960 (a primary source from 1997 -- twenty years old -- and PMID 16359583, a review that is from 2007, ten years old, but is probably OK
• diff at 14:09, 16 March 2017 via IP 128.231.234.33 you restored that last one, fixing the formatting of the two refs and adding a third, PMID 9269249 which is a literature review from 1997 and too old.
• diff at 14:50, 16 March 2017 via IP 128.231.234.33 you restored it again.

The first five times you added this, it was reverted for being unsourced alone. The sixth time, it was reverted because you made a mess. The last two times, because the sources are bad and you have not come to Talk page even once to say why you think the symptoms should be listed in this article. Any number of people may have been happy to help with that. The symptoms are listed (and sourced) in the "main" article SSRI discontinuation syndrome which is linked prominently in that section. Jytdog (talk) 19:46, 16 March 2017 (UTC)

Discontinuation syndrome/Withdrawal symptoms

Dear all, I would like to propose several edits to the "discontinuation syndrome" section. For one, the term "discontinuation syndrome" term is a Wyeth/Pfizer-created term. The widely accepted term for symptoms after discontinuation of a drug is "withdrawal symptoms", so this is the title this section should have, to avoid confusion and misinterpretation by a potential patient reading the article.

Regarding the listing of symptoms in the section: While the section links to the "SSRI discontinuation syndrome", where the symptoms are stated, this is misleading, given that the prevalence and degree of symptoms is higher for venlafaxine than other SSRIs, such as e.g. fluoxetine or sertraline. (see these references: J Clin Psychiatry. 2005 Oct;66(10):1312-20. Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. Sir A, D'Souza RF, Uguz S, George T, Vahip S, Hopwood M, Martin AJ, Lam W, Burt T. Aust N Z J Psychiatry. 1998 Apr;32(2):291-4. Withdrawal reactions associated with venlafaxine. Parker G, Blennerhassett J. J Psychopharmacol. 2008 May;22(3):330-2. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. Tint A, Haddad PM, Anderson IM.)

Therefore, linking to the general "SSRI discontinuation syndrome" is not sufficient in this case, especially since the "SSRI discontinuation syndrome" page does not list the documented rate of venlafaxine withdrawal symptoms and how it differs from other SSRIs. I would therefore like to not only add the symptoms, but also highlight that the withdrawal symptoms experienced after discontinuation of venlafaxine are of a different nature than e.g. withdrawal from fluoxetine.

Furthermore, I would like to point out that even the Wikipedia article for fluoxetine (Prozac), lists the symptoms of withdrawal, despite linking to "withdrawal syndrome" in the same paragraph: "If stopped suddenly a withdrawal syndrome may occur with anxiety, dizziness, and changes in sensation.[1]"

Additionally, I would like to add a paragraph stating that there need for a study investigating prevalence of venlafaxine withdrawal effects, as noted in the 2006 consensus ("Antidepressant Discontinuation Syndrome: Current Perspectives and Consensus Recommendations for Management," Journal of Clinical Psychiatry, 2006).

In response to some of the edits removing the references I had included: > here, diff at 13:51, 16 March 2017 via IP 128.231.234.33 you finally provided 2 refs; both misformatted. The two refs are PMID 9396960 (a primary source from 1997 -- twenty years old -- and > PMID 16359583, a review that is from 2007, ten years old, but is probably OK > diff at 14:09, 16 March 2017 via IP 128.231.234.33 you restored that last one, fixing the formatting of the two refs and adding a third, PMID 9269249 which is a literature review from 1997 and too > old.

Deleting a reference because it is "too old" is highly questionable. Research done in 1997 can be cited. If there is a newer study demonstrating that the 1997 study was false that reference may be included.

> The first five times you added this, it was reverted for being unsourced alone. The sixth time, it was reverted because you made a mess. The last two times, because the sources are bad and you > have not come to Talk page even once to say why you think the symptoms should be listed in this article. Any number of people may have been happy to help with that. The symptoms are listed > (and sourced) in the "main" article SSRI discontinuation syndrome which is linked prominently in that section. Jytdog (talk) 19:46, 16 March 2017 (UTC)

Again, deleting a reference because "it is bad" is questionable. If there are scientifically founded concerns with the references, I'm happy to discuss those.

Looking forward to hearing from you. — Preceding unsigned comment added by Noaanon (talk • contribs) 12:36, 20 March 2017 (UTC)

Thanks for talking. WP:MEDRS is a guideline that is widely accepted in the community, for very many reasons. The sources you are bringing are not OK here in WP for this kind of content. The kind of content being proposed would be good. The sourcing matters, as does the process. Jytdog (talk) 23:19, 20 March 2017 (UTC)

Pharmacokinetics

The Pharmacokinetics part of this page says: "It is extensively metabolized in the liver via the CYP2D6 isoenzyme to desvenlafaxine (O-desmethylvenlafaxine), which is just as potent a SNRI as the parent compound, meaning that the differences in metabolism between extensive and poor metabolisers are not clinically important in terms of efficacy. Side effects, however, are reported to be more severe in CYP2D6 poor metabolisers."

This statement is not true.

My suggestion for this part is: "It is extensively metabolized in the liver via the CYP2D6 isoenzyme to desvenlafaxine (O-desmethylvenlafaxine),therefore, the CYP2D6 enzyme activity determines the systemic exposure (AUC and Cmax) of venlafaxine and the active moieties (venlafaxine+O-desmethylvenlafaxine), which are significantly higher in CYP2D6 poor metabolizers than in CYP2D6 extensive metabolizers. Although O-desmethylvenlafaxine is just as potent a SNRI as the parent compound, and the exposure of active moieties (venlafaxine+O-desmethylvenlafaxine)is much higher in CYP2D6 poor metabolizers, they show much lower venlafaxine efficacyand more side effects,compared to CYP2D6 extensive metabolizers.

Sounds interesting. I don't suppose there is a metaanalysis on this topic? If not, per WP:MEDREV, you should include the information that these data are from just 100 / 33 / 24 patients. --ἀνυπόδητος (talk) 13:49, 22 March 2017 (UTC)

References

Semi-protected edit request on 18 January 2019

Venlafaxine has an opioid method of action in addition to being an SNRI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171132/ https://www.ncbi.nlm.nih.gov/pubmed/11931344 https://www.ncbi.nlm.nih.gov/pubmed/15157989 https://www.ncbi.nlm.nih.gov/pubmed/10505622

Mwiner (talk) 03:13, 18 January 2019 (UTC)

The article already says that here:Venlafaxine#Pharmacology --Literaturegeek | T@1k? 03:26, 18 January 2019 (UTC)

Very much undue weight to try to add that to the lead. Even in the body we need better references. Doc James (talk · contribs · email) 16:18, 18 January 2019 (UTC)

Okay found some better refs. Doc James (talk · contribs · email) 16:29, 18 January 2019 (UTC)

Mechanism

Ref says "Mechanisms of antidepressant and anxiolytic actions are uncertain"[1]

Which can be summarized as "How it works is not entirely clear" Doc James (talk · contribs · email) 04:30, 20 January 2019 (UTC)

Full quote on mechanism

Ref says "Mechanisms of antidepressant and anxiolytic actions are uncertain but appear to be associated with the potentiation of neurotransmitter activity in the CNS. Venlafaxine and ODV are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake"

The summary leaves out most of the statement, and oversimplifies what's left.--ScottS (talk) 17:59, 20 January 2019 (UTC)

If we compare this to the information that the same reference website provides on the mechanism of another anti-depressant, Escitalopram, a similar statement is made--that the mechanism is not fully understood. Yet the Wikipedia page for Escitalopram doesn't mention that piece of information.

As I've stated in other correspondence about inconsistent coverage on the subject of prescription medication by Wikipedia; my concern is that laymen like myself who want to compare two anti-depressants using Wikipedia might be steered in one direction or another simply because of the inconsistency of how they're summarized in Wikipedia. --ScottS (talk) 18:42, 20 January 2019 (UTC)

User:ScottSloe I have added "... but it is believed to involve alterations in neurotransmitters in the brain" Doc James (talk · contribs · email) 19:54, 21 January 2019 (UTC)

Toxic levels found in deceased tramper

A coroner's report into the death of a Czech tramper in New Zealand found "toxic" (13 mg/L blood) levels of Velafaxine. The report found the death was due to hypothermia, relating to poor decisions to attempt the route while under-prepared, but I think this snippet is relevant and should be included, as depression and anti-depressants can affect decision making processes. The coroner's report includes other findings from a forensic toxicologist, and also says that such high concentrations can cause cardiac arrhythmias, which "may" have contributed to the death from hypothermia.

• https://www.scribd.com/document/424184919/Coronial-finding-for-Ondrej-Petr
• https://www.stuff.co.nz/national/115457620/czech-couples-decisionmaking-on-deadly-great-walk-tramp-criticised — Preceding unsigned comment added by Foobar2k20 (talk • contribs) 08:19, 3 September 2019 (UTC)

Chart showing IC50 values should also show Desvenlafaxine

The activate metabolite Desvenlafaxine contributes significantly to the activity of Venlafaxine. I think the table showing the Ki and IC50 values should show it for both Venlafaxine and Desvenlafaxine. Links to those values here and here, but I can not figure out how to correctly reformat the table. — Preceding unsigned comment added by SSyntaxin (talk • contribs) 20:20, 19 October 2019 (UTC)

I've added the data to Desvenlafaxine. Thanks for bringing this up! --ἀνυπόδητος (talk) 09:07, 20 October 2019 (UTC)

Challenge Editor DocJames to a Debate

DocJames has repeatedly blocked any and all attempts to put the opioid method of action for Venlafaxine at the top of this article. The related opioid Tramadol lists SNRI activity at the top despite Tramadol not being officially classified as an SNRI. Venlafaxine lists opioid methods of action three times in the body but not at all in the top section. DocJames is appealing to Western Medical dogmatic thinking which suggests that only the classified use of a drug needs be mentioned. Perhaps DocJames is unaware that there are other methodologies for medicine besides Western Medicine? Perhaps DocJames is aware that not only doctors interact with medications but patients do as well? Why can't patients edit Wikipedia? Maybe patient input is important? Why are these (non-medical) editors being blocked?

The debate... DocJames is lording his medical degree over the rest of us (as advertised on his wiki page). If his medical training is so good (he's an emerg doc, according to wiki page), let him debate the issue publicly and not hide behind repeated bans of my account.

Debate question: Codeine and Morphine differ by 1 carbon atom. The extra carbon of Codeine is demethylated in the liver. This extra processing step makes codeine the 'weaker' opioid because it is less immediately bioavailable. Note that I was able to provide a clear and concise biochemical explanation as to the difference between Codeine and Morphine.

Please review: https://www.researchgate.net/profile/Justin_Barber3/publication/50998428/figure/fig1/AS:394259501993984@1471010198062/Molecular-Structures-of-venlafaxine-and-tramadol-From-Venlafaxine-Tramadol.png

Tramadol and Venlafaxine also differ by 1 carbon atom. What is the exact biochemical explanation (like the one I provided for Codeine/Morphine) which explains why Venlafaxine is neither a mu1 binding opioid nor an NMDA antagonist whereas Tramadol is both?

(p.s. here's why this debate matters: https://www.ncbi.nlm.nih.gov/pubmed/31637686 ) — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:C8B4:976A:437B:B56 (talk) 07:03, 23 January 2020 (UTC)

Answer me here DocJames, stop hiding behind user bans. — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:C8B4:976A:437B:B56 (talk) 06:50, 23 January 2020 (UTC)

The main body states in the pharmacology section that venlafaxine’s affect on the opioid system is indirect, so that alone would suggest that it is not an opioid drug. Also, an opioid mechanism would need to be significantly strong and occur at therapeutic doses to describe it as an opioid, especially in the article lead.

Actually, Doc James medical credential carry zero weight on Wikipedia in content disputes, and venlafaxine is a psychiatric drug so Doc James is not editing within his area of expertise anyway. The reason your edits are getting reverted is because they are of poor quality — you are using old sources, single case reports, individual animal studies and other primary sources. Instead you should be obtaining high quality and recent sources for your edits, e.g., review articles, systematic review articles and meta-analyses etc., per WP:MEDRS. Doctors do tend to interpret medical literature better than lay editors, such as yourself, by nature of their training etc., but layperson editors with better sources will always win the argument. You should read more about how Wikipedia works if you want to progress here.--Literaturegeek | T@1k? 02:02, 24 January 2020 (UTC)

Poor resources? https://books.google.ca/books?id=sEFyDwAAQBAJ&pg=PA73&dq=venlafaxine+opioid&hl=en&sa=X&ved=0ahUKEwiFvJWS4_fmAhVsp1kKHUE1DZkQ6AEIKTAA#v=onepage&q=venlafaxine%20opioid&f=false A textbook?

Literature Geek: Venlafaxine and Tramadol differ by only one carbon atom. What is the exact biochemical reason that Venlafaxine is neither a mu1 binding opioid nor an NMDA antagonist whereas Tramadol is both?

EveryoneElse: Notice that I've received a non answer to my question (Venlafaxine vs Tramadol) This will occur over and over again with pretentious Wikipeia editors who know nothing about nothing. Will anyone answer my question? If you can't you're injuring patients by concealing Venlafaxine's opioid method of action. — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:247F:54CF:D553:4D05 (talk) 02:15, 24 January 2020 (UTC)

Drugs work like keys in a lock, you can change one small detail in a key and it might still open the door or the change in pattern may mean it no longer opens that door but might open a different door. Trying to predict the effects of a drug based on chemical diagrams is not ideal, to say the least, for the reasons I have just explained. There needs to be rigorous studies. So that is your “debate questions” answered.

Please provide a high quality source for your edits that specifically classifies venlafaxine as an opioid. Do you have a high quality source that says: venlafaxine is an opioid? At the moment your edits do not have supporting sources that classify venlafaxine as an opioid so your edits are being reverted, per WP:NOR and WP:WEIGHT.--Literaturegeek | T@1k? 02:44, 24 January 2020 (UTC)

Yes, your text book source is a better source, when I first clicked on it I got a message saying the page was not available but it is available to me now.--Literaturegeek | T@1k? 02:49, 24 January 2020 (UTC)

"The antinociceptive properties of venlafaine and mirtazapine in mice have been attributed to opioid receptor activation with vanlafaxine's effects mediated via MOP (mu1 opioid), KOP and DOP"

https://books.google.ca/books?id=sEFyDwAAQBAJ&pg=PA73&dq=venlafaxine+opioid&hl=en&sa=X&ved=0ahUKEwiFvJWS4_fmAhVsp1kKHUE1DZkQ6AEIKTAA#v=onepage&q=venlafaxine%20opioid&f=false

Page 73

"OPIOID RECEPTOR ACTIVATION" That's it! You can't argue further. A textbook lists venlafaxine as working via opioid receptor activation, not indirectly, not downstream... opioid receptor activation. That's an opioid. Period. — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:247F:54CF:D553:4D05 (talk) 03:22, 24 January 2020 (UTC)

>> Drugs work like keys in a lock, Absolutely false. Any nitrogen center 2 or 3 atoms away from a phenol group will likely indicate opioid activity. Don't trust me. Google H.H. Hennies... the inventor of Tramadol. It's his quote You absolutely did not answer my debate question. — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:247F:54CF:D553:4D05 (talk) 03:25, 24 January 2020 (UTC)

https://www.researchgate.net/publication/20306198_Receptor_binding_analgesic_and_antitussive_potency_of_tramadol_and_other_selected_opioids page 877, first line..

"Despite the ample variability in the structure of opioids, most compounds that behave as narcotic analgesics contain an aromatic ring system spaced from a basic nitrogen center by a group of 2 or 3 atoms..."

Not lock and key. False. Please stop editting articles you don't know anything about. — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:247F:54CF:D553:4D05 (talk) 03:36, 24 January 2020 (UTC)

“Will likely” not “will definitely”, “most compounds...” not “all compounds” so I did answer your question accurately, anyway please also see, WP:NOTFORUM. Working in (probably venlafaxine mega overdosed) mice via opioid mechanism, but what about humans at normal dosage? Venlafaxine actives many serotonin receptors without touching them via blocking the reuptake of serotonin (serotonin itself activates serotonin receptors) so just because venlafaxine activates opioid receptors does not mean that it does so directly. You seem to only partially understand what you are writing. In fairness it is indeed plausible that venlafaxine will work similarly to tramadol in opioid activity, at least the mechanism of action. The key question is do you have a source to say that venlafaxine actives opioid receptors at therapeutic doses and do you have a source that classifies venlafaxine as an opioid? No source means no edit. Your original research of synthesising sources might be correct but original research is against Wikipedia rules, see WP:NOR, particularly WP:SYN.--Literaturegeek | T@1k? 03:44, 24 January 2020 (UTC)

I have provided a source for LiteratureGeek which flat out says that Venlafaxine works by OPIOID RECPTOR ACTIVATION. LiteratureGeek is doing what all wiki editors do, engage in semantic battles when they've lost on logical bases.

LiteratureGeek says drugs are lock and key. I blew that out of the water (see above). Then he said I didn't have a good source... I blew that out of the water (see above). He's now Bill Clintoning and saying that Venlafaxine goes to the opioid receptors but perhaps it doesn't inhale. I will engage in no more conversation with LiteratureGeek because he isn't engaging in debate... he's engaging in "I'm right, you're wrong".

The question remains: Venlafaxine and Tramadol differ by one carbon atom only. Thanks to LiteratureGeek we know that structurally similarity is hugely important in opioid activiy. What is the exact biochemical reason that Venlafaxine is neither a mu1 binding opioid nor an NMDA antagonist whereas Tramadol is both? If you can't answer, don't answer, keep quiet. Lesson for wikikedia editors, keep your mouths shut, you open them too often and are always in error.

Who will debate me next, someone who edits veterinary pages? — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:247F:54CF:D553:4D05 (talk) 04:46, 24 January 2020 (UTC)

It does not matter what you think or I think. Wikipedia goes by what sources say. If you do not have a source that specifically classifies venlafaxine as an opioid then it does not get added to Wikipedia. You are doing ignoring of arguments yourself. I pointed out the opioid effect of venlafaxine might only occur at very high doses (overdoses) and that a single mouse study does not cut it. You have not provided a source saying that this effect occurs at therapeutic doses in humans. You can create a blog and add your WP:SYN there, just not here.--Literaturegeek | T@1k? 05:11, 24 January 2020 (UTC)

LiteratureGeek is making up the rules as he goes along. I've provided a source, a TEXTBOOK!!! Again it says: "OPIOID RECEPTOR ACTIVATION". This is unambiguous. It only means one thing. The fact that it refers to a mouse model is inconsequential. It refers to multiple studies if you had bothered to read it. Not just one mouse study. It is in a Academic Text that says "Opioids are good targets for depression" and this is the chapter about how Effexor(Venlafaxine) is one of them! READ!

By the way, mice studies are how opioids are tested. Is LiteratureGeek going to volunteer for a human opioid study where they dissect his brain after a few weeks of exposure? LiteratureGeek needs to go to the Tramadol page. There he'll discover that it lists Tramadol's SNRI activity right up top. He'll then follow the links and realize that it's the same level of 'proof' or verifiability that I've provided for Venlafaxine being an opioid. Is LiteratureGeek going to remove the SNRI activity from the top of Tramadol because it was done on mice?

The question remains: Venlafaxine and Tramadol differ by one carbon atom only. Thanks to LiteratureGeek we know that structurally similarity is hugely important in opioid activiy. What is the exact biochemical reason that Venlafaxine is neither a mu1 binding opioid nor an NMDA antagonist whereas Tramadol is both? (a) the added carbon of Venlafaxine masks the activity of the phenyl group and hence it doesn't bind (b) the added carbon of Venlafaxine changes the polarity of the molecule such that it no longer binds (c) the added carbon of Venlafaxine causes Venlafaxine to mirror a known antigen and is removed by the immune system when close to opioid receptors (d) the added carbon of Venlafaxine causes a 'folded chair' configuration of the cyclohexane ring and blocks binding. (e) there is no significant difference between Venlafaxine and Tramadol. Both bind similarly. This wasn't detected due to dogmatic thinking and silo'ed development of both drugs and silo'ed approval and safety measures. — Preceding unsigned comment added by 2607:FEA8:3CA0:3CD:247F:54CF:D553:4D05 (talk) 06:41, 24 January 2020 (UTC)