Tiafentanil (A-3080), similar in structure to sufentanil, is used in veterinary medicine as a safer alternative to carfentanil (therapeutic index is x48 versus x16 for carfentanil). Experiments to immobilize animals with tiafentanil and similar opioids were conducted at Salt Lake City University in collaboration with the Edgewood Chemical Research, Development and Technology Center (ERDEC).
Remifentanil is a top-synthetic analgesic of the fentanyl group, first synthesized in 1991 by Glaxo Pharmaceuticals and now available under the brand name Ultiva.
In the human body, remifentanil is rapidly degraded by plasma esterases and therefore has the shortest duration of action among the opioids used. Loss of consciousness after injection of remifentanil is very quick, occurring within 30 seconds after the injection and no later than 5-10 minutes later the drug is also quickly terminated.
Taking into consideration the high therapeutic index of remifentanil, the new analgesic could not be ignored by the developers of non-lethal chemical weapons. It was assumed that when remifentanil was used as an incapacitant, its action would pass so quickly that a person would not have time to develop severe respiratory distress.
A 1994 report prepared by C.P. Ferguson, technical director of the Edgewood Chemical Research, Development and Technology Center (ERDEC), stated that synthetic opioids, such as remifentanil, should be considered prime candidates for use as non-lethal chemical agents.
According to the document, fast-acting fentanyls have already been synthesized in the ERDEC laboratory and have undergone preliminary toxicological evaluations. In 2001, the Office of Chemical and Biological Defense Forces (USASBC-COM) conducted experimental work to evaluate the feasibility of remifentanil as an immobilizing agent.
For many years, carfentanil was rightfully considered the strongest of the biologically active substances synthesized by man and was even entered in the Guinness Book of Records. But in 1991, at the same time as remifentanil, Glaxo synthesized even more powerful analgesic from this group, exceeding carfentanil by 25 times. The chemical structure of this substance is remifentanil, in which the end methyl group has been replaced by the tretbutyl group.
According to the document, fast-acting fentanyls have already been synthesized in the ERDEC laboratory and have undergone preliminary toxicological evaluations. In 2001, the Office of Chemical and Biological Defense Forces (USASBC-COM) conducted experimental work to evaluate the feasibility of remifentanil as an immobilizing agent.
For many years, carfentanil was rightfully considered the strongest of the biologically active substances synthesized by man and was even entered in the Guinness Book of Records. But in 1991, at the same time as remifentanil, Glaxo synthesized even more powerful analgesic from this group, exceeding carfentanil by 25 times. The chemical structure of this substance is remifentanil, in which the end methyl group has been replaced by the tretbutyl group.
The analgesic dose of this substance in mice was only 0.021 µg/kg versus 0.52 µg/kg for the former leader carfentanil. The duration of analgesia is about 1.5 hours, which makes this substance of little use as an incapacitant.
Czech researchers have experimented with intranasal and conjunctival routes of administration of remifentanil. These routes can be useful for rapid analgesia in a large number of victims (in disasters, accidents, etc.).
Research on fentanyl-group incapacitants in various countries
China. The PRC has always been considered one of the world leaders in the synthesis and study of the most active thebaine and phenylpiperidine derivatives, and now it seems that they have also achieved outstanding success in improving the rapid action of drugs for human and animal immobilization.
China is the only country that has produced a commercial sample "syringe gun" for military and police use, called "tranquiliser gun BBQ-901", which allows you to immobilize an enemy at a distance of up to 40 meters. According to the manufacturer, they managed to achieve impressive speed, after hitting "the target can not move and offer resistance in less than a minute.
In earlier models, the time before immobilization was specified between 1 and 3 minutes and depended on the anesthetic chosen and on which part of the body the syringe hit. The effect of the anesthetic injection begins to diminish after 3 to 4 minutes.
Czech researchers have experimented with intranasal and conjunctival routes of administration of remifentanil. These routes can be useful for rapid analgesia in a large number of victims (in disasters, accidents, etc.).
Research on fentanyl-group incapacitants in various countries
China. The PRC has always been considered one of the world leaders in the synthesis and study of the most active thebaine and phenylpiperidine derivatives, and now it seems that they have also achieved outstanding success in improving the rapid action of drugs for human and animal immobilization.
China is the only country that has produced a commercial sample "syringe gun" for military and police use, called "tranquiliser gun BBQ-901", which allows you to immobilize an enemy at a distance of up to 40 meters. According to the manufacturer, they managed to achieve impressive speed, after hitting "the target can not move and offer resistance in less than a minute.
In earlier models, the time before immobilization was specified between 1 and 3 minutes and depended on the anesthetic chosen and on which part of the body the syringe hit. The effect of the anesthetic injection begins to diminish after 3 to 4 minutes.
According to the British Defense Studies Laboratory (DSTL), "vinyl-carfentanil" synthesized in 1990 at the Beijing Institute of Pharmaceutical Chemistry, could be of potential military interest. "Vinyl-carfentanil" is approximately equal in activity to carfentanil, but its two analogs numbered 1379 and 1387 surpass it by 1.6 and 2 times, respectively. Work on the activity and synthesis of carfentanil and ochmecarfentanil derivatives was carried out at Nanjing Military Hospital in 1992-1993.
Czech Republic. In 1985, Czech physician Ladislav Hess received 1 gram of the powerful new analgesic carfentanil from the pharmaceutical company Janssen, which was tested on three staff volunteers. At a dose of 0.25 µg/kg, carfentanil caused analgesia, sedation, and sleep when administered intramuscularly and intranasally, but even this "homeopathic" dose reduced respiratory rate by half.
Until 1989, the Czechoslovak Socialist Republic was a member of the Warsaw Treaty Organization and, together with the USSR, was developing new types of non-lethal chemical weapons. After the disintegration of Czechoslovakia and its accession to NATO, after a long pause, in the early 2000s the Czech Republic resumed work on "pharmacological non-lethal weapons".
In 2005, at the III European Symposium on Non-Lethal Weapons, a group of Czech scientists presented a report on the inhalation effects of various formulations, including those based on remifentanil, sufentanil and alfentanil, on rats. These experiments confirmed the fact that these fentanyls do not have a high speed of action - the depressing effect of such aerosols on animals became noticeable only after a 10-minute exposure.
According to data obtained by Czech scientists, ultra-powerful opioids such as carfentanil and sufentanil completely suppress aggression in experimental animals, which is a very important quality for modern incapacitants.
Until 1989, the Czechoslovak Socialist Republic was a member of the Warsaw Treaty Organization and, together with the USSR, was developing new types of non-lethal chemical weapons. After the disintegration of Czechoslovakia and its accession to NATO, after a long pause, in the early 2000s the Czech Republic resumed work on "pharmacological non-lethal weapons".
In 2005, at the III European Symposium on Non-Lethal Weapons, a group of Czech scientists presented a report on the inhalation effects of various formulations, including those based on remifentanil, sufentanil and alfentanil, on rats. These experiments confirmed the fact that these fentanyls do not have a high speed of action - the depressing effect of such aerosols on animals became noticeable only after a 10-minute exposure.
According to data obtained by Czech scientists, ultra-powerful opioids such as carfentanil and sufentanil completely suppress aggression in experimental animals, which is a very important quality for modern incapacitants.
India. Since the 2010s, the Defense Research and Development Organization of the Indian Ministry of Defense (DRDO) has also shown increased interest in fentanyl derivatives. Opioid analgesics synthesized by Indian chemists have a high safety index and are as active as fentanyl. However, judging by publications in the open press, significant results have not yet been achieved.
DRDO is also working to simplify and reduce the cost of obtaining fentanyl, using the so-called "one-pot" synthesis, that is, without isolating the intermediate products. Studies on thermal sublimation and various methods of determination of fentanyls in the environment are underway.
DRDO is also working to simplify and reduce the cost of obtaining fentanyl, using the so-called "one-pot" synthesis, that is, without isolating the intermediate products. Studies on thermal sublimation and various methods of determination of fentanyls in the environment are underway.
Iran. Imam Hussein University studied the relationship between the activity and chemical structure of 70 fentanyl derivatives. Iranian chemists were interested in the effect of different pharmacophore groups on analgesic activity.
South Africa. In the early 1990s, South Africa was searching for "narcotic incapacitants" from the fentanyl group. At least four fentanyl derivatives were synthesized and tested on mice without much success.
USA. In the United States, experiments on the effects of aerosol on primates were conducted in the 1980s, but their results have never been published, since most of the documents concerning the development of new incapacitants of this group are still classified as "secret". For example, one of the papers published by Edgewood Chemical Research, Development and Technology Center (ERDEC) in 1992 provides data on the activity of more than 60 fentanyl derivatives, but some information, probably related to the most promising compounds, is still removed from the publication.
In the early 1990s, ERDEC attempted to synthesize carfentanil derivatives that would combine the properties of an opioid receptor agonist and antagonist. Drugs in this class, such as buprenorphine and butorphanol, have a relatively high therapeutic index for opiates and rarely cause fatal overdose. However, the synthesized cyclopropyl and allyl analogues of carfentanil had no safety advantage over the already known fentanyls.
South Africa. In the early 1990s, South Africa was searching for "narcotic incapacitants" from the fentanyl group. At least four fentanyl derivatives were synthesized and tested on mice without much success.
USA. In the United States, experiments on the effects of aerosol on primates were conducted in the 1980s, but their results have never been published, since most of the documents concerning the development of new incapacitants of this group are still classified as "secret". For example, one of the papers published by Edgewood Chemical Research, Development and Technology Center (ERDEC) in 1992 provides data on the activity of more than 60 fentanyl derivatives, but some information, probably related to the most promising compounds, is still removed from the publication.
In the early 1990s, ERDEC attempted to synthesize carfentanil derivatives that would combine the properties of an opioid receptor agonist and antagonist. Drugs in this class, such as buprenorphine and butorphanol, have a relatively high therapeutic index for opiates and rarely cause fatal overdose. However, the synthesized cyclopropyl and allyl analogues of carfentanil had no safety advantage over the already known fentanyls.
In 1993, 2-fluoroanilido derivatives of carfentanil, alfentanil and sufentanil were synthesized at ERDEC, perhaps the most interesting group of opioid incapacitants. In experiments on mice, fluorocarfentanil was 25% less toxic and 7 times more active than carfentanil. At the same time, its safety index (LD50) was 8 times higher than that of carfentanil.
According to unconfirmed official reports, in 2001 U.S. special forces used carfentanil aerosol to storm the Tora Bora cave complex in northern Afghanistan, which the Taliban had turned into an impregnable underground fortress.
China: undeclared chemical warfare
Because of the extremely small single drug dose, carfentanil is ideal for drug trafficking - 1 kg of carfentanil is equivalent to 4 tons of heroin. In the past decade, illegal carfentanil has spread rapidly across the United States and Western Europe. By 2016, carfentanil ranked fourth among fentanyl derivatives detected in drug samples submitted to U.S. crime labs.
In the United States, carphenanil accounts for more than half of fentanyl derivative overdose deaths. In 2016, 389 people in 10 U.S. states alone were victims of fatal carfentanil overdoses in a 6-month period.
In the European Union, carfentanil became illegal in late 2012, at virtually the same time as in Eastern Europe - the first deaths due to carfentanil overdoses were reported in Belarus that same year. The Baltic States had the highest number of seizures of carfentanil by the police, but the United Kingdom had the highest number of deaths, with the largest seizure of 440 grams of carfentanil made in the United Kingdom.
According to unconfirmed official reports, in 2001 U.S. special forces used carfentanil aerosol to storm the Tora Bora cave complex in northern Afghanistan, which the Taliban had turned into an impregnable underground fortress.
China: undeclared chemical warfare
Because of the extremely small single drug dose, carfentanil is ideal for drug trafficking - 1 kg of carfentanil is equivalent to 4 tons of heroin. In the past decade, illegal carfentanil has spread rapidly across the United States and Western Europe. By 2016, carfentanil ranked fourth among fentanyl derivatives detected in drug samples submitted to U.S. crime labs.
In the United States, carphenanil accounts for more than half of fentanyl derivative overdose deaths. In 2016, 389 people in 10 U.S. states alone were victims of fatal carfentanil overdoses in a 6-month period.
In the European Union, carfentanil became illegal in late 2012, at virtually the same time as in Eastern Europe - the first deaths due to carfentanil overdoses were reported in Belarus that same year. The Baltic States had the highest number of seizures of carfentanil by the police, but the United Kingdom had the highest number of deaths, with the largest seizure of 440 grams of carfentanil made in the United Kingdom.
«Indeed, carfentanil is the ideal terrorist weapon. It is readily available in large quantities. It comes in several forms - including pills, powder and spray. It can be absorbed through the skin or by inhalation. It works quickly» - Michael J. Morell, former director of the CIA.
A serious terrorist threat is the ease with which large quantities of carfentanil can be acquired from Chinese chemical companies. An Associated Press investigation titled "Chemical Weapons for Sale: China's Uncontrolled Drug," published in 2016, found that at least 12 Chinese firms are willing to export carfentanil for as little as $2,750 per kilogram. China's Ministry of Public Security, however, declined to comment on the matter.
Estimates published earlier suggest that about 3 kilograms of the substance, worth $15,000, are needed to "put the entire U.S. population to «sleep».
A serious terrorist threat is the ease with which large quantities of carfentanil can be acquired from Chinese chemical companies. An Associated Press investigation titled "Chemical Weapons for Sale: China's Uncontrolled Drug," published in 2016, found that at least 12 Chinese firms are willing to export carfentanil for as little as $2,750 per kilogram. China's Ministry of Public Security, however, declined to comment on the matter.
Estimates published earlier suggest that about 3 kilograms of the substance, worth $15,000, are needed to "put the entire U.S. population to «sleep».
