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The supposed Super potent Analgesic W-18 &its little brother W-15 Are not Opioid

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Alchemyst:
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

Alchemyst:
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.

Vesp:
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?

Alchemyst:
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.
--- End quote ---

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

asdet0281:
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.

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