More on W-18's pharmacology

Another update on Twitter by Dr. Bryan Roth from Roth Lab at UNC - Chapel Hill...

W18 predicted by SEA only H3 histamine activity. No predicted opioid activities

— BryanRoth(@zenbrainest) May 21, 2016

@drugmonkeyblog we will post all data this week on bioarchivxas getting lots of media requests for info

— BryanRoth(@zenbrainest) May 21, 2016

So, no predicted opioid activities again. Only histamine H3 receptor activity. And data will be posted on Bioarchivx sometime this coming week!

Ain't social media great?

W-18 Associated Fatality Reported in Calgary

It was reported today in the Calgary Herald that a 35 year old man was found deceased at a Calgary hotel on March 7, 2016. The death was believed to be drug-related at the time. Law enforcement found drugs, paraphernalia, and a naloxone kit (albeit unusued) on the scene.

The Herald reports that the individual had "heroin, W-18, and 3-methylfentanyl" in his system when he died.

The article gives some "fast facts on W-18". They include:

"The drug is said by police  to be 100 times more potent than fentanyl."

My thoughts?

First, I'm glad I'm not a forensic pathologist. And cause and manner of death is obviously the pathologist's responsibility. It is her call to make.

Second, from a toxicology perspective, I'd be more focused on 3-methylfentanyl (known potent mu opioid receptor agonist) and heroin (prodrug for 6-acetylmorphine and morphine) than the W-18 (at this point). Especially considering what we know about W-18 - that the 10,000 times more potent than morphine and 100 times more potent than fentanyl trope comes from a mouse model writhing assay - and what we officially unofficially know about W-18 - not an opioid receptor agonist.

Interesting article. Still we should be very, very careful on how we talk about W-18. Hysteria and hyperbole is not the way to go. Talk about what we do know. Talk about what we do not know. But misrepresenting facts in not ok. The headline of the article only includes W-18. That is misrepresenting the situation at hand. This is a death that was associated with all three compounds.


Reference:

Medical examiner confirms city's first fatal W-18 overdose

W-18 Pharmacology Update

From the last post on W-18, we should remember that other than the mouse writing assay data, we know nothing about the pharmacology of the substance. NOTHING.

 

Chemical structure of W-18

Well, that's changed a bit. At least officially unofficially.

Dr. Brian Roth (@zenbrainest) of Roth Lab in the Department of Pharmacology at the University of North Carolina - Chapel Hill tweeted a few days ago that they had preliminary information on W-18 via the NIMH Psychoactive Drug Screening Program.

Regarding W-18 and possible activity at mu opioid receptors...

@rgcjk @forensictoxguy We have no evidence for mu receptor activity....

— BryanRoth (@zenbrainest) May 11, 2016

And what about activity at kappa and delta opioid receptors?

@andcunningham @rgcjk @forensictoxguy No activity there. Compound seems quite toxic (unknown target) which is problematic for some assays.

— BryanRoth (@zenbrainest) May 11, 2016

And toxicity at what cells?

@drugmonkeyblog @andcunningham @rgcjk @forensictoxguy HEK cells though I wouldn't be surprised if others also toxic

— BryanRoth(@zenbrainest) May 11, 2016

So, there you have it. Officially unofficially W-18 has no activity at the mu, kappa, or delta opioid receptors.