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Etonitazene (CS 4640)


The CIA and the US Department of Defense, who were closely monitoring the appearance of new chemicals with high biological activity, were able to get samples of etonitazene at their disposal as soon as possible. At the CIA, it was studied by Harris Isbell from the National Institute of Mental Health. In 1954-1964, X. Isbell was attracted by the US Central Intelligence Agency to work on the MK-Pilot project, which is part of the more extensive MK-Ultra program, which was engaged, among other things, in the search for substances that cause rapid addiction, knockout, increase suggestibility and the like. The experiments were conducted on drug addicts in a rehabilitation center in Lexington (Kentucky) under the guise of a national program to search for new painkillers. All data on human trials of 800 drugs, including the recently discovered etonitazen, were promptly transmitted to the CIA.

Etonitazene (CS 4640)

Experiments on humans disappointed the researchers a little — etonitazen was not as powerful as expected, analgesia and euphoria similar to morphine occurred when ingested or subcutaneously administered 0.25 mg of the drug. In fact, etonitazene was not 1000 times stronger than morphine, but “only” 60-100 times.

The speed and high activity of etonitazene, so necessary for CIA operatives to immobilize the enemy, did not interest the pharmacists, for them the main factor was the safety of the drug for the patient. And just with this, everything was not so smooth with etonitazen, even a small overdose caused respiratory depression, and long-term use led to drug addiction.

In the end, the CIA also considered etonitazen too dangerous to use against people, although they continued to use it to neutralize guard dogs during special operations. At first, ordinary capsules with ethonitazene were used for this, which were mixed into the feed. To prevent the appearance of a sleeping dog from arousing suspicion, an antidote was included with the capsules, which made it possible to quickly bring the animal to life after the operation.

Etonitazene (CS 4640)

Later, for these purposes, in the 60s, the CIA, together with army specialists, developed a special cartridge for a standard 7.62 mm cartridge designed for firing needle bullets, or as they were also called “micro-missiles”. The M-1 micro-missiles were one of five types of biological sabotage weapons, also known as the “Big Five”, developed by the Special Operations Division (SOD). Made of steel and platinum, such a “micro-rocket” had a diameter of 0.25 mm and a length of 25 mm, and its tip was coated with gelatin containing 3 mg of ethonitazene[18]. This amount was enough to put the dog to sleep for 4-6 hours, but for a person such a dose could be fatal. At least four modifications of such “micro-missiles” were produced for the US Army, including for the M-1 rifle and the M209 pistol, in which ethonitazene was replaced with deadly poisons, such as, for example, botulinum toxin (XR), saxitoxin or a combination of them.

Later, a more advanced model of such a weapon was developed — the E-1/M-1 electric pistol, it was almost silent, and the Javettes needle bullets fired from it quickly and painlessly dissolved into the human body, leaving no traces. Even if a person noticed the hit of such a bullet, he still would not have a chance to get rid of it.

The Edgewood Center for Chemical Research, Development and Technology (ERDEC) initially enthusiastically accepted the new encapsulator. Numerous experiments were conducted on mice, rats, guinea pigs, rabbits, cats, dogs, goats and monkeys.

In 1959, for members of the US Congressional committee overseeing the development of chemical and biological weapons, a demonstration was conducted of the effects of an aerosol of 0.1% etonitazene solution on two dogs. After half a minute, the animals began to relax and after one minute they were completely immobilized. After 10 minutes, one of the dogs was injected with an antidote, after which the animal completely returned to normal within a few minutes. The second dog, who did not receive the antidote, also fully recovered after an hour’s sleep.

However, after a short burst of hopes for a quick receipt of an effective and safe encapsulator, disappointment followed. Further experiments showed that safe for rodents, etonitazene turned out to be too toxic for primates. Nevertheless, his toxicological tests at the Edgewood Arsenal were so large-scale that they even caused protests from the International Primate Protection League (IPPL) — a very large number of monkeys died during experiments to determine the lethal dose of etonitazene.

As a result, all known attempts to create a safer encapsulator based on its molecule failed — the slightest change in the structure led to a drop in activity. The drug under the code EA 2664, like etonitazene, was first synthesized in the Swiss company CIBA in 1958 and was the only known drug of this group having an activity comparable to etonitazene, but it turned out to be more toxic. The earlier data obtained that the EA 4232 precursor was allegedly as powerful analgesic as etonitazen were also not confirmed.

Only a few benzimidazole derivatives gave some hope. As it turned out, the introduction of a hydroxyl group into the methylene bridge, not only did not reduce the activity, but also reduced the toxicity. The p-methoxy homologue of etonitazene synthesized in 1960 with a hydroxyl group in the CH-bridge, as an analgesic, was slightly inferior to etonitazene, but turned out to be 20 times less toxic. On its basis, in the early 60s, a number of derivatives were synthesized at ERDEC, of which the substance under the code EA 5270 is of the greatest interest. It was assumed that one of its isomers could surpass etonitazene in activity and safety.

The formula of another encapsulator from the group of benzimdazoles is given in the Soviet textbook on military toxicology (V. N. Alexandrov, V. I. Yemelyanov, 1990), without reference to the source. The authors of the manual claim that this drug has an immobilizing effect at a dose of 0.001 mg/kg and that its “toxodose is three orders of magnitude higher than the disabling one”. However, according to the data of Swiss pharmacologists, a substance with such a structure is only 10 times more active than morphine. But its 5-nitro derivative, indeed, is 200 times more active than morphine, but only in mice.

Many more opioid encapsulants in the history remain a mystery and, probably, etonitazen was not the most powerful of the analgesics known in those years. In addition to the MK-Pilot subroutine mentioned above, which was engaged in collecting information about potential candidates for toxic substances in the United States, the CIA had another, no less secret MK-Chickwit program, the purpose of which was to monitor substances with high or unusual biological activity synthesized by pharmaceutical companies in Europe and Asia, as well as to obtain prototypes of such drugs. In 1958, an interesting meeting took place. Isbell (H. Isbell) and the famous Belgian pharmacologist P. Janssen (P. Janssen). The conversation was about new benzimidazole derivatives, and P. Janssen told a colleague that he had managed to synthesize new drugs with amazing analgesic activity. One of them was 3,000 times more powerful than morphine in experiments on monkeys, and the other, ” a rather unstable fluorinated derivative, was 300,000 times, more powerful than morphine.” The US military Chemical Center already knew about new analgesics and X. Isbell expected to receive samples for testing on volunteers in the near future.

In 1997, illegal sales of etonitazen were registered in Germany, and in 1998 — in Russia. In Moscow, in 1998, the first underground laboratory for the production of ethonitazene was liquidated. The drug, dubbed the “white dwarf”, caused the deaths of 18 people in just a few months. The power of this drug was so great that to get a “dose” it was enough to smoke a cigarette, inside of which there was a thin cotton thread soaked with ethonitazene. And even the ashes of such a cigarette still remained active — even if smoked repeatedly, it facilitated withdrawal in drug addicts.

In 2003, Thomas Highsmith, a chemist working in the Salt Lake City laboratory, synthesized etonitazene and began taking it in the form of a nasal spray. After a few months of constant intake, he needed a daily dose 300 times higher than the initial one. The strange behavior of the employee, who did not part for a minute with a bottle of spray for a cold, forced colleagues to contact the police. Since the detainee was not engaged in the sale of drugs, the police did not arrest him until the court decision. However, unable to resist drug addiction, Thomas Highsmith committed suicide without waiting for the verdict.

In 2019, almost simultaneously, in the USA, Canada, Belgium and Australia, Isotonitazene (Isotonitazene), an o — isopropyl homologue of etonitazene, appeared on the designer drug market. This analgesic in animal experiments was only 2 times inferior in activity to etonitazene.