Sciencemadness Discussion Board

Less-than-lethal (LTL) anesthetic CW agents

Ritter - 13-7-2008 at 12:29

One of the U.S. Army's CW R&D programs has been directed at studying Less-Than-Lethal (LTL) anesthetics for potential military applications. Many may recall the Russians using a knockout gas to subdue a major hostage situation some years ago.

It is public knowledge that the Army became intererested in a compound with the generic name medetomidine. This is a solid small-molecule anesthetic & analgesic used in large animal surgery. An extensive amount of R&D effort involving the Edgewood Arsaenal, the U.S. Navy & 2 university groups led to a potent analog of medetomidine that was published about 12 years ago here:
Quote:
J. Med. Chem., 39 (15), 3001 -3013, 1996


and US patent 5151526. The structures of both medetomidine & the chiral naphthalene analog are shown in the ChemDraw attachment.

[Edited on 13-7-2008 by Ritter]

medetomidine.gif - 8kB

Ritter - 13-7-2008 at 13:33

Attached is an outline of the U.S. Army patent route to the naphthalene analog. It is relatively simple (as drug syntheses go) but yield is low & a couple of the reagents & intermediates are not commonly available.

medetomidine analog Army patent process.gif - 10kB

ShadowWarrior4444 - 13-7-2008 at 13:50

I seem to recall that Russian 'knockout gas' was a diluted nerve agent that killed half the people in the theater. Not that I mind though, it was quite efficient.

It would be interesting if there was a useful anesthetic with an ED50 below its LD50. Do you have any reports on the effectiveness of this compound?

PainKilla - 13-7-2008 at 14:23

The agent that the Russians used (some fentanyl analogue) that actually has quite a high therapeutic index (as most opiods do). The problem was that the medics were not prepared to treat the opiod-induced respiratory depression. Were they so, I imagine that there would have been much fewer casaulties.

In general, I think the opiods are definitely among the best non-lethal weapons.

[Edited on 13-7-2008 by PainKilla]

Ritter - 13-7-2008 at 19:14

Quote:
Originally posted by PainKilla
The agent that the Russians used (some fentanyl analogue) that actually has quite a high therapeutic index (as most opiods do). The problem was that the medics were not prepared to treat the opiod-induced respiratory depression. Were they so, I imagine that there would have been much fewer casaulties.

In general, I think the opiods are definitely among the best non-lethal weapons.

[Edited on 13-7-2008 by PainKilla]


There are a number of references stating that the Russian agent was etorphine, a potent thebaine derivative opioid.

PainKilla - 13-7-2008 at 19:55

I've read carfentanyl; but it's useless speculation anyway. In either case, it was a very potent mu-opioid receptor agonist.

[Edited on 13-7-2008 by PainKilla]

Sauron - 14-7-2008 at 00:35

All reports as to the identity of the Russian opioid agent are speculative. What is the ED50 or etorphine, relative to carfentanyl? Obviously whatever the agent was, its ED50 was close to its LD50 and I would classify it as not very LTL as it killed a high proportion of the hostages.

Etorphine is a semisynthetic derivative or morphine. It is said to be 10,000 X more potent subcutaneously than morphine, which is in same order of magnitude as carfentanyl. Both are used to immobilize elephants and other large mammals by veterinarians. They are both very dangerous to handle and their use requires special training.

The US has a LTL agent which induces orthostatic hypotension. It is a synthetic cannabinoid analog. I could tell you exactly, but then I'd have to kill you (as the old joke goes.) Seriously I think this structure has been divulged, possibly in one of those NAP reports. I don't recall the exact structure off the top of my head, but I have it somewhere.

Orthostatic hypotension means that the agent induces a sudden sharp drop in blood pressure, resulting in extreme fatigue or unconsciousness. If one is standing he will collapse, if sitting he won't be able to stand, and in either case won't have the strength to raise his arm to fire a weapon. As always there are certain delicate considerations having to do with use in a hostage rescue operation, but I won't prattle on about these as they have nothing to do with amateur chemistry.


[Edited on 14-7-2008 by Sauron]

Methyl.Magic - 14-7-2008 at 11:04

I think it is Carfentanyl for sure because it synthesis looks much more simple than etorphine and wikipedia says that it is probably a fentanyl analogue.

ShadowWarrior4444 - 14-7-2008 at 12:07

Quote:
Originally posted by Sauron
The US has a LTL agent which induces orthostatic hypotension. It is a synthetic cannabinoid analog. I could tell you exactly, but then I'd have to kill you (as the old joke goes.) Seriously I think this structure has been divulged, possibly in one of those NAP reports. I don't recall the exact structure off the top of my head, but I have it somewhere.
[Edited on 14-7-2008 by Sauron]


Nabilone; Compound 109514; Lilly-109514
dry mouth (80%), dizziness (80%), orthostatic hypotension (53%), euphoria (20%)



A single dose study of nabilone, a synthetic cannabinoid
Journal: Psychopharmacology
Publisher: Springer Berlin / Heidelberg
ISSN: 0033-3158 (Print) 1432-2072 (Online)
Issue: Volume 71, Number 2 / November, 1980
Category: Original Investigations
DOI: 10.1007/BF00434401
Pages: 137-142
Subject: Collection Biomedical and Life Sciences

[Or some other similar analog that I can't quite recall at the moment.]



The Russian agent was most certainly a fentanyl analog if I recall correctly. Fentanyls are quite popular these days; even moussad has a fetish for using them.

Perhaps the Russians were testing a new p-fluorofentanyl compound! *giggles* (Or maybe they just gave a little injection of etomidate to the people they didn’t want to live.)

[Edited on 7-14-2008 by ShadowWarrior4444]

franklyn - 14-7-2008 at 20:27

The agent in the Russian debacle was fentanyl. Those exposed died of
respiratory depression.The reason why an anesthesiologist must monitor its use.

http://news.bbc.co.uk/1/hi/world/europe/2377563.stm
http://en.wikipedia.org/wiki/Moscow_theater_hostage_crisis
http://en.wikipedia.org/wiki/Fentanyl
http://cns.miis.edu/pubs/week/02110b.htm

A host of incapacitating agents have been investigated over the years,
hypnotics, deliriants and hallucinogens. Benzodiazepines (BZ) are used as a clinical
psychotropics, the cryptic nomenclature only hints at the class of compound it is.
I recall a recreational psychotropic unkindly street named " Jerry's Kids " because
it makes you feel retarded, was likely of this type.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pccompound&t...

.

Sauron - 14-7-2008 at 20:58

The military incap agent BZ was not a benzodiazapine.

It is quite explicitly quinuclidin-3-yl benzilate. It binds to muscarinereceptor sites, and induces auditory and visual hallucinations similar to those produced by high doses of datura alkaloids (atropine etc) only much more severe and longer lasting. Its counteragent is tetrahydroacridine.

BZ was produced in vast quantities, weaponized and stockpil;ed by the US and is now being destroyed.

Some relatives of BZ were tried as street drugs without success.

The effects of BZ are described as unplesant and terrifying.

Sauron - 14-7-2008 at 21:09

Both carfentanyl and some of its very potent analogs, and also etorphine, could have been used, and both could have had the same effect (operation was succesful but 60% of patients died.)

So unless the Russians have identified what they actually used, which they have not, the answer is indeterminate. The media are just guessing, by talking to some boffin who is no more and possibly less qualified than the boffins I talk to. As for Wiki...well, that's Wiki.

Carfentanyl happens to be my best guess, and that of my sources. But etorphine is also a distinct possibility.

Yes "car" is easier to make, but etorphine is also simple to make if you have a source of thebaine or the chemical from poppy straw that is its precursor. No one said the agent was totally synthetic.

We previously encountered clandestine use of carfentanyl in the assassination of Pakistan PM Zia. The Russians were high on the short list of suspects.

Ritter - 15-7-2008 at 05:45

Quote:
Originally posted by Sauron
Both carfentanyl and some of its very potent analogs, and also etorphine, could have been used, and both could have had the same effect (operation was succesful but 60% of patients died.)



The speculation is that the Russian's had not prepared to respond with the antidote, naloxone.

Sauron - 15-7-2008 at 08:04

Bottom line was: kill the terrorists, and Marx will sort out the hostages. Very Cromwellian attitude the Kremlin has.

dr. nick - 15-7-2008 at 11:54

got one, too:

Ditran

a Mix of 70 % N-Ethyl-3-piperidyl-phenyl-cyclopentyl-glycolat und 30 % N-Ethyl-2-pyrrolidylmethyl-phenyl-cyclopentyl-glycolat.

Works via the muscarinergic receptors, too, and seems to be a real mean bad trip, as far as i could find out.

Ritter - 17-7-2008 at 05:49

Quote:
Originally posted by dr. nick
got one, too:

Ditran

a Mix of 70 % N-Ethyl-3-piperidyl-phenyl-cyclopentyl-glycolat und 30 % N-Ethyl-2-pyrrolidylmethyl-phenyl-cyclopentyl-glycolat.

Works via the muscarinergic receptors, too, and seems to be a real mean bad trip, as far as i could find out.


Ditran was discussed in the thread 'More on CW agent codes.' You could have found that if you had used the Search function before posting.

Sauron - 17-7-2008 at 06:17

That "mixture" only formed if a short cut in the manufacturing process was unwisely made.

This problem was corrected early on. Ditran properly is only the piperidine compound.

The missing step was a high vacuum distillation. Carrying that out of the mixture reconverted the impurity to the proper structure.

Bad trip, very, by all accounts, which is why it was of military interest for a while and why it was a disaster as a street drug.

Ritter - 17-7-2008 at 06:50

Quote:
Originally posted by Sauron
That "mixture" only formed if a short cut in the manufacturing process was unwisely made.

This problem was corrected early on. Ditran properly is only the piperidine compound.

The missing step was a high vacuum distillation. Carrying that out of the mixture reconverted the impurity to the proper structure.

Bad trip, very, by all accounts, which is why it was of military interest for a while and why it was a disaster as a street drug.


Even marijuana can produce a 'bad trip' (dysphoria as opposed to euphoria). I learned this from a former Pfizer medicinal chemist who had synthesized some very potent cannabanoid analogs that bore no resemblance to any naturally-occurring cannabanoid.

dr. nick - 17-7-2008 at 12:43

Quote:
Even marijuana can produce a 'bad trip' (dysphoria as opposed to euphoria

of course it can. know a guy that after 20 years of smoking experienced heavy
anxiousness attacks that didn't wore off anymore just after the thc stopped to work
and are continually recurring since then although he stopped smoking for years now.
if you ever experienced a real (one you really can't handle anymore - everything else
is just a little fear) panic attack you know why it's of interest for the military ...
(*ugh*)
that, of course, is not the norm, but i can happen to some people.
Quote:
Ditran was discussed in the thread 'More on CW agent codes.' You could have found that if you had used the Search function before posting.


huh? why should i have searched for it? i just mentioned it here as e.g BZ was mentioned before.

ok, maybe it's not anaesthetic, or what do you mean?
i mean, it should be definitely LTL by it self :)


[Edited on 17-7-2008 by dr. nick]

Skrinkle - 18-7-2008 at 09:59

Quote:
Originally posted by PainKilla
I've read carfentanyl; but it's useless speculation anyway. In either case, it was a very potent mu-opioid receptor agonist.

[Edited on 13-7-2008 by PainKilla]





I agree. i remember hearing that it was an aerosolized form of either carfentanyl of plain fentanyl.

If it were me, I would use a stimulant combined with either,
1: A choline inhibiting delierent
or
2: A serotonergic/adrenergic hallucinogen such as 2c-e, or a potent mescaline analogue if my intention was to incite a panic attack.

Sauron - 18-7-2008 at 21:31

Good thing it's not you then. Such things have been thoroughly investigated for hostage rescue applications and found completely unsuitable.

dr. nick - 19-7-2008 at 02:10

like in that case in russia of course it's probably not desirable to a induce heavy psychosis and panic in both the hostages and the heavily armed hostage takers, especially while both parties caged and barricaded in one room ...

btw: not a weapon thing (afaik) , but can anyone remember - there where some newspaper anouncements on south america some years ago. they reported there was used some kind of spray on tourists that made them so aboulic they could be manipulated to draw all their money, give it to the sprayers and wheren't able to remember afterwards?

was that just a hoax?

[Edited on 19-7-2008 by dr. nick]

Sauron - 19-7-2008 at 02:39

Never heard of that, but it does sound like a tall tale.

Where was that supposed to have happened?