3-Quinuclidinyl benzilate (QNB) (IUPAC name 1-azabicyclo .2.2ctan-3-yl hydroxy(diphenyl)acetate;

US Army The United States Army (USA) is the land service branch of the United States Armed Forces. It is one of the eight U.S. uniformed services, and is designated as the Army of the United States in the U.S. Constitution.Article II, section 2, cla ...

code EA-2277;

NATO The North Atlantic Treaty Organization (NATO, ; french: Organisation du traité de l'Atlantique nord, ), also called the North Atlantic Alliance, is an intergovernmental military alliance between 30 member states – 28 European and two No ...

code BZ; Soviet code Substance 78) is an odorless and bitter-tasting military

incapacitating agent The term incapacitating agent is defined by the United States Department of Defense as: :"An agent that produces temporary physiological or mental effects, or both, which will render individuals incapable of concerted effort in the performance o ...

.QNB: Incapacitating Agent
Emergency Response Safety and Health Database
National Institute for Occupational Safety and Health. Accessed April 20, 2009. BZ is an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

s whose structure is the

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

benzilic acid Benzilic acid is an organic compound with formula or ()2(HO)C(COOH). It is a white crystalline aromatic acid, soluble in many primary alcohols. Preparation Benzilic acid can be prepared by a heating mixture of benzil, ethanol, and potassium hy ...

with an

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

derived from

quinuclidine Quinuclidine is an organic compound and a bicyclic amine and used as a catalyst and a chemical building block. It is a strong base with p''K''a of the conjugate acid of 11.0.{{cite journal , title=Azatriquinanes: Synthesis, Structure, and Reacti ...

Physiochemical characteristics

BZ is a white crystalline powder with a bitter taste. It is odorless and nonirritating with delayed symptoms several hours after contact. It is stable in most solvents, with a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

of three to four weeks in moist air; even heat-producing munitions can disperse it. It is extremely persistent in soil and water and on most surfaces. BZ is soluble in water, soluble in dilute acids,

trichloroethylene The chemical compound trichloroethylene is a halocarbon commonly used as an industrial solvent. It is a clear, colourless non-flammable liquid with a chloroform-like sweet smell. It should not be confused with the similar 1,1,1-trichloroethane, ...

dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the majo ...

, and most organic solvents, and insoluble with aqueous alkali.

Effects

As a powerful

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

agent, BZ produces a

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...

of effects known as the anticholinergic toxidrome: these include both psychological and physiological effects, with the most incapacitating effect being a state of

delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...

characterized by

cognitive dysfunction Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem solving. Neurocognitive disorders in ...

hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...

, and inability to perform basic tasks. The usual syndrome of physical anticholinergic effects are also present, including

mydriasis Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, as ...

(potentially to the point of temporary

blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

, dermal

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

xerostomia Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side ef ...

and

hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...

. The readily-observable symptoms of the anticholinergic toxidrome are famously characterized by the

mnemonic A mnemonic ( ) device, or memory device, is any learning technique that aids information retention or retrieval (remembering) in the human memory for better understanding. Mnemonics make use of elaborative encoding, retrieval cues, and imag ...

"Mad as a hatter, red as a beet, dry as a bone and blind as a bat" (and variations thereof).

Toxicity

Based on data from more than 500 reported cases of accidental atropine overdose and deliberate poisoning, the median lethal oral dose is estimated to be approximately 450 mg (with a shallow probit slope of 1.8). Some estimates of lethality with BZ have been grossly erroneous, and ultimately the safety margin for BZ is inconclusive due to lack of human data at higher dosage ranges, though some researchers have estimated it to be 0.5 to 3.0 mg/kg and an LD₀₁ is 0.2 to 1.4 mg/kg (Rosenblatt, Dacre, Shiotsuka, & Rowlett, 1977).

Treatment

Antidotes An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

for BZ include 7-MEOTA, which can be administered in tablet or injection form.

Atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...

and

tacrine Tacrine is a centrally acting acetylcholinesterase inhibitor and indirect cholinergic agonist (parasympathomimetic). It was the first centrally acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed un ...

(THA) have also been used as treatments, THA having been shown to reduce the effects of BZ within minutes. Some military references suggest the use of

physostigmine Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...

to temporarily increase synaptic acetylcholine concentrations.

History

Invention and research

BZ was invented by the Swiss

pharmaceutical company The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...

Hoffman-LaRoche in 1951. The company was investigating anti-spasmodic agents, similar to

tropine Tropine is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol. Tropine is a central building block of many chemicals active in the nervous system, including tropane alkaloids. Some of these comp ...

, for treating gastrointestinal ailments when the chemical was discovered. It was then investigated for possible use in ulcer treatment, but was found unsuitable. At this time the United States military investigated it along with a wide range of possible nonlethal, psychoactive and

psychotomimetic A drug with psychotomimetic (also known as psychotogenic) actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to only hallucinations. Psychotomimesis is the onset of psychotic symptoms following the administrat ...

incapacitating agents including

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...

s such as

LSD Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...

and

THC Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

drugs such as

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...

and

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptio ...

, potent

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

s such as

fentanyl Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocaine ...

, as well as several glycolate

anticholinergics Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

. By 1959, the

United States Army The United States Army (USA) is the land service branch of the United States Armed Forces. It is one of the eight U.S. uniformed services, and is designated as the Army of the United States in the U.S. Constitution.Article II, section 2, cla ...

showed significant interest in deploying it as a chemical warfare agent. It was originally designated "TK", but when it was standardized by the Army in 1961, it received the NATO code name "BZ", the Chemical Corps initially referred to BZ as CS4030, then later as EA 2277. The agent commonly became known as "Buzz" because of this abbreviation and the effects it had on the mental state of the human volunteers intoxicated with it in research studies at

Edgewood Arsenal Aberdeen Proving Ground (APG) (sometimes erroneously called Aberdeen Proving ''Grounds'') is a U.S. Army facility located adjacent to Aberdeen, Harford County, Maryland, United States. More than 7,500 civilians and 5,000 military personnel work a ...

in Maryland.Kirby, Reid.
Paradise Lost: The Psycho Agents
, ''The CBW Conventions Bulletin'', May 2006, Issue no. 71, pp. 2-3, accessed December 11, 2008. As described in retired Army psychiatrist James Ketchum's autobiographical book ''Chemical Warfare: Secrets Almost Forgotten'' (2006), work proceeded in 1964 when a general envisioned a scheme to incapacitate an entire trawler with aerosolized BZ; this effort was dubbed Project DORK. BZ was ultimately weaponized for delivery in the

M44 generator cluster The M44 generator cluster was an American chemical cluster bomb designed to deliver the incapacitating agent BZ. It was first mass-produced in 1962 and all stocks of the weapons were destroyed by 1989. History The United States Army Chemical Corp ...

and the M43 cluster bomb, until all such stocks were destroyed in 1989 as part of a general downsizing of the US chemical warfare program. In 2022 a documentary film, '' Dr Delirium and The Edgewood Experiments'', was broadcast on

Discovery+ Discovery may refer to: * Discovery (observation), observing or finding something unknown * Discovery (fiction), a character's learning something unknown * Discovery (law), a process in courts of law relating to evidence Discovery, The Discover ...

, featuring an interview with Ketchum not previously shown.

Use and alleged use

In February 1998, the British

Ministry of Defence {{unsourced, date=February 2021 A ministry of defence or defense (see spelling differences), also known as a department of defence or defense, is an often-used name for the part of a government responsible for matters of defence, found in states ...

accused

Iraq Iraq,; ku, عێراق, translit=Êraq officially the Republic of Iraq, '; ku, کۆماری عێراق, translit=Komarî Êraq is a country in Western Asia. It is bordered by Turkey to Iraq–Turkey border, the north, Iran to Iran–Iraq ...

of having stockpiled large amounts of a

glycolate Glycolic acid (or hydroxyacetic acid; chemical formula HOCH2CO2H) is a colorless, odorless and hygroscopic crystalline solid, highly soluble in water. It is used in various skin-care products. Glycolic acid is widespread in nature. A glycolate (so ...

incapacitating agent known as ‘Agent 15’. Agent 15 is an alleged Iraqi incapacitating agent that is likely to be chemically identical to BZ or closely related to it. Agent 15 was reportedly stockpiled in large quantities prior to and during the

Persian Gulf War The Gulf War was a 1990–1991 armed campaign waged by a 35-country military coalition in response to the Iraqi invasion of Kuwait. Spearheaded by the United States, the coalition's efforts against Iraq were carried out in two key phases: ...

. However, after the war the

CIA The Central Intelligence Agency (CIA ), known informally as the Agency and historically as the Company, is a civilian intelligence agency, foreign intelligence service of the federal government of the United States, officially tasked with gat ...

concluded that Iraq had not stockpiled or weaponized Agent 15. According to Konstantin Anokhin, professor at the Institute of Normal Physiology in Moscow, BZ was the chemical agent used to incapacitate terrorists during the 2002 Nord-Ost siege, but 204 hostages perished due to overdose; but many other agents have also been proposed, and none definitively confirmed. In January 2013, an unidentified U.S. administration official, referring to an undisclosed U.S. State Department cable, claimed that "Syrian contacts made a compelling case that Agent 15, a hallucinogenic chemical similar to BZ, was used in

Homs Homs ( , , , ; ar, حِمْص / ALA-LC: ; Levantine Arabic: / ''Ḥomṣ'' ), known in pre-Islamic Syria as Emesa ( ; grc, Ἔμεσα, Émesa), is a city in western Syria and the capital of the Homs Governorate. It is Metres above sea level ...

". However, in response to these reports a

U.S. National Security Council The United States National Security Council (NSC) is the principal forum used by the President of the United States for consideration of national security, military, and foreign policy matters. Based in the White House, it is part of the Exe ...

spokesman stated,

"The reporting we have seen from media sources regarding alleged chemical weapons incidents in Syria has not been consistent with what we believe to be true about the Syrian chemical weapons program".

Legality

BZ is listed as a Schedule 2 compound by the OPCW (Szinicz, 2005).

Footnotes

References

External links

Erowid
��BZ Vault

��Incapacitating Agents: 3-Quinuclidinyl Benzilate

Center for Disease Control
��BZ Incapacitating Agent
Paradise Lost: The Psycho Agents by Reid Kirby

Department of Defense
��Agent BZ use in Hawaii April through June 1966. {{DEFAULTSORT:Quinuclidinyl Benzilate, 3- Muscarinic antagonists Carboxylate esters Deliriants Incapacitating agents 3-Quinuclidinyl esters Chemical weapons of the United States Swiss inventions Tertiary alcohols Benzilate esters