Author Topic: The supposed Super potent Analgesic W-18 &its little brother W-15 Are not Opioid  (Read 174224 times)

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Offline Alchemyst

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PHARMACOLOGY OF W-18 AND W-15

Xi-Ping Huang, Tao Che, Thomas Mangano, Valerie Le Rouzic, Ying-Xian Pan, Susruta Majumdar, Michael Cameron, Michael Bauman, Gavril Pasternak, Bryan L Roth

doi: https://doi.org/10.1101/065623



Abstract

W-18 (1-(4-Nitrophenylethyl)piperidylidene-2-(4-chlorophenyl)sulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide) represent two emerging drugs of abuse chemically related to the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide). Here we describe the comprehensive pharmacological profiles of W-18 and W-15. Although W-18 and W-15 have been described as having potent anti-nociceptive activity and are presumed to interact with opioid receptors, we found them to be without detectible opioid activity at ?, ?, ? and nociception opioid receptors in a variety of assays. We also tested W-18 and W-15 for activity as allosteric modulators at opioid receptors and found them devoid of significant positive or negative allosteric modulatory activity. Comprehensive profiling at essentially all the druggable G-protein coupled receptors in the human genome using the PRESTO-Tango platform revealed no significant activity. In silico predictions using the Similarity Ensemble Approach suggested activity for W-18 only weakly at H3-histamine receptors, which was not confirmed in radioligand binding studies. Weak activity at the sigma receptors and the peripheral benzodiazepine receptor were found for W-18 (Ki=271 nM); W-15 displayed weak antagonist activity at 5-HT2-family serotonin receptors. W-18 is extensively metabolized, but its metabolites also lack opioid activity. W-18 and W-15 did inhibit hERG binding suggesting possible cardiovascular side-effects with high doses. Thus although W-18 and W-15 have been suggested to be potent opioid agonists, our results reveal no significant activity at these or other known targets for psychoactive drugs.

I can't upload a file, i think my connection is too slow and the site don't accept it because its too long idk so i'll post the link :
https://www.biorxiv.org/content/biorxiv/early/2016/07/24/065623.full.pdf
« Last Edit: February 28, 2018, 09:55:17 AM by Alchemyst »

Offline Alchemyst

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I thought maybe dealers have ordered tons of this compound !!  ;D ;D ;D :o :o :o :'( :'( :'(
Because it has already been found in Canada in pills containing only W-18 and others where it was mixed with fentanyl.

Offline Vesp

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Wow, crazy! Do they produce enjoyable effects? Or the same breathing suppression and unconsciousness effects as opioids or do they just kill pain entirely without all the other aspects of opioids?
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Offline Alchemyst

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Apparently they are totally devoid of any effect nor analgesic nor sedative nor euphoriant, read the paper for more info (its not a big paper you can read it really fastly)


Quote
This led law enforcement officials, Health Canada and the media to initially–and mistakenly–describe the drug as an opioid. But the comparison to morphine in the patent was made in a relatively non-specific mouse model of pain where other classes of pain relievers (analgesics) and unrelated drugs show effectiveness. The drug has never been evaluated in humans.

The then-graduate student who made the compounds told me in April that he and the two other inventors had never tested the chemicals as opioids and had only preliminary evidence that the painkilling effects could be reversed by the opioid antagonist naloxone (Narcan; Adapt Pharma). But no further work on W-18 or its relatives was published by the inventors or other researchers since the patent.

Source : https://www.forbes.com/sites/davidkroll/2016/07/28/w-18-is-not-a-super-potent-designer-opioid-as-originally-believed/#ddfb14c6333f

Best joke of the years, they could had waited the 1st april, But i don't understand why the team who Publied the first paper on those compound hasn't said anything since some decade.

Edit: I see the article date from 2016 and nobody noticed that until i found this totally by hazard.

And we can see how people lie in trip report, i'm pratically sure to have read some trip report on W-18 and W-15
« Last Edit: February 28, 2018, 01:28:17 PM by Alchemyst »

Offline asdet0281

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ive read the paper but ive tried w-15 and it was the crapiest opioid i ever had, the 4-chloro just makes no sense from a qsar standpoint. but its got definetively some mu activity, despite what this paper says.

Offline d00d

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Might as well give the DSIP peptide a go.  Supposed to have bite, 'the next harm reduction tool' they say.
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Offline middleman_eu

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Sadly due the current catastrophic scene regarding the RCs Opioids, where It's still debatable if the cause of this situation / who is more guilty can have a lot of arguments to compile a pretty long list between:
a) the government and the prohibitionism strategy to contain an opioid pandemic started many many years a go in USA
b) the greedy way chinese pretended to ""save"" the scene
c) the totally obsolete philosophy / rule adapted by tradition from all existing (dark) markets
- and try to identify who actually is responsible for the biggest number of countless deaths, a comeback of violence and criminality in the streets, and leaving patients with chronic pains who did nothing wrong, but regardless now they must life in permanent painful conditions - were the very small % lucky enough to keep his prescription - is tied now from a mutually exclusive rule that they CAN'T have any psychological disease in terms of anxiety or severe insomnia (doctor could be insta-jailed if he will prescribe to a patient with any opioid script, any benzo, even a single pill of zolpidem) -

The fact the myth of W15-W18 and any other fantasy codename you will read on countless of clearnet websites, are actually super-effective and potent and find a lot of reviews on reddit and other places confirming it - 99.5% of such it's because the current situation and recent ban in february of a class with several analogues that wildspread in the last 3 years - generated new opportunities to promote based on such myths and the many reviews, the misinformation of such compounds to actually be functional, and if they weren't before, it was because they did it wrong.
No need to say, the 99.5% of such reviews, it's simply because they bought something with such name, victims of the marketing and what search engines are giving back as results, that contained obviously a mix of different other strong opioids (and just checking energycontrol recent drugs check results, even 2-3 different drugs family and traces of leftovers of whatever else).

If there is a possible working W-1X chemical that is actually matching to the original structure declared when such compounds were listed many years a go from the researchers who wrote the paper, it's still a mystery, and most likely like the OP says, not even opioid (in terms of chemistry structure) - same for kratom, tianeptine, and the several RB-1XX (Enkaphalin Inhibitors) that had a boom in research papers as well available from some companies, the so-called Opioids 2.0, where no overdose, no withdrawal, no tolerance increase is possible (but with a potential analgesic potency up to 80x) - of course without any recreational value, but it would have at least saved the category of chronic pain patients who had not much choice if living in pain, or taking the path of unknown and RCs where the WIDE choice available is either something like O-DSMT (less stronger than morphine, but for some people was definitely better than nothing), and the next step, without anything in between with a legal status, 70x (now not even legal anymore).

Sorry the the long off-topics ;)