New drug called W-18

Is this another fake scare, or are people actually dying from it? Also, why is it legal?

It’s legal because nothing has made it illegal. Chemicals start out legal until legislated otherwise. Some chemicals are specifically illegal, like heroin. This leads chemists to synthesize chemicals that are very similar structurally to the banned substances, because they’ll probably have similar effects, and if they’re new, then they’re not specifically banned yet. That’s typically what’s meant by “designer drugs”.

In the USA, the government tried to fight proliferation of designer drugs with the Federal Analogue Act, which bans not specific chemicals, but entire classes of chemicals, if they make good recreational drugs and they’re sold for human consumption. This leads chemists to search even farther afield, for chemicals that have the desired effects and aren’t in any way similar to existing drugs of abuse. That seems to be what has happened here. W-18 will presumably get banned too; Canada seems to already be working on that. The game will continue.

This game of regulatory whack-a-mole is dangerous, because it pushes drug traffickers away from chemicals that, while not exactly safe, have known characteristics, and probably won’t immediately kill you outright. Heroin addiction, for example, isn’t good for you, but is also very survivable long-term, if the addict has a reliable supply of the drug of known purity. New drugs have unknown side effects. Highly potent drugs like that W-18 are specially attractive to traffickers, because one easy-to-smuggle package is potentially a huge number of doses.

They’re also specially dangerous, because few drug dealers have the lab skills to reliably dilute the drug into the form that will be sold on the street: they might intend to make ten doses of 100 ug each, but accidentally make one dose of 900 ug and nine doses of 11 ug, resulting in nine disappointed customers and one dead one. (Those numbers are fake; I don’t know what the dose is for W-18. The general idea still holds.)

I personally take this as more evidence that prohibition, beyond causing addicts to fund Mexican beheadings, also probably isn’t helping public health. This of course is heavily debated.

But its a fentanyl analogue.

"You take fentanyl and replace the terminal phenyl with pyridyl. Here is the abstract. "

The patent makes it clear * about numerous other analogues.

(* as clear as a black hole. )

Interesting point, and fentanyl is Schedule 2, right? So that would seem to fall under the Federal Analogue Act, if the two have a chemical structure that is “substantially similar”. It’s not like they just tacked on a methyl group, but I do see the similarity. But the article says:

So maybe they’re just different enough that the DA didn’t want to waste time arguing about that in court, when they already had the guy on the fentanyl, and it’s less “legal” and more “undetermined”? Or maybe the story is just wrong, since that’s unreferenced?

Actually, it looks like your underground chemist’s description was intended to apply to other of Knaus’s opiates, and that he considered W-18 as a member of a new class?

In any case, I think I found the Florida importer, caught with 2.5 pounds of a drug that may have first come to illicit attention through the Russian chemical weapons literature… If that’s pure, that’s basically an infinite supply, limited only by their ability to market the stuff.

Yes, the quote referred to another molecule. W-18 is clearly inspired by the fentanyls but is a couple of steps away, maintains the N-phenethyl-piperidine ring but has swapped the typical amidyl nitrogen in the 4-position with a sufonylamidine-type group in the 2 position - very substantial change. There are no rules as to whether this constitutes a different ‘class’, chemically speaking, just a matter of semantics really.
Pharmacological classes would be more clearly defined, as it either hits the same opioid receptor with the same mechanism, or it doesn’t, and this should be straightforward to quanitfy for such a well-studied class of receptor.

So is that chemist’s comment that the new molecules “do not contain a single protonated nitrogen” a reference to some kind of known binding mechanism for fentanyls, and an implication that the new compounds work differently?

2.5 pounds of the stuff sure seems like overkill. If it’s 10000x as potent as morphine, and heroin is 5x as potent as morphine, and a heroin user takes a usual dose around 10 mg, then a usual dose of W-18 would be ~5 ug, so that’s ~200 million doses. But I guess they’re expecting their customers to develop a much higher tolerance than a heroin user would reach? If that means they’re no longer affected by normal doses of other opioids, then maybe that’s an advantage from the trafficker’s standpoint, because it locks the customers in?

He’s commenting on the different forms of nitrogen functionality just in general terms - The fentanyls feature an amine nitrogen in the 6-membered ring, which is basic enough to be predominately protonated at physiological pH. Matey appears to be saying that the arylamidine in W-18 is considerably less basic so it is not protonated in vivo. This is a significant difference that could effect binding, distribution, metabolism etc.

This doesn’t seem quite right to my chemist’s eye as I’d expect the amidine to still be comfortably basic enough to be protonated at phys pH [although it is protonated on the exocyclic N, not the ring N]. Overall, though, it is obv quite an altered structure so could easily work through a different mechanism.