BZ "Agent Buzz" 3-Quinuclidinyl benzilate

Russia Today reported 14 April 2018 "The substance used on Sergei Skripal was an agent called BZ, according to Swiss state Spiez lab, the Russian foreign minister said. The toxin was never produced in Russia, but was in service in the US, UK, and other NATO states. Sergei Skripal, a former Russian double agent, and his daughter Yulia were poisoned with an incapacitating toxin known as 3-Quinuclidinyl benzilate or BZ, Russian Foreign Minister Sergey Lavrov said, citing the results of the examination conducted by a Swiss chemical lab that worked with the samples that London handed over to the Organisation for the Prohibition of the Chemical Weapons (OPCW)."

"Based on the results of the examination, traces of the toxic chemical BZ and its precursors, related to chemical weapons of the second category in accordance with the Convention on the Prohibition of Chemical Weapons, were found in the samples. BZ is a nerve agent temporarily disabling a person. The effect is achieved within 30-60 minutes and lasts up to four days," Lavrov said.

Maryland's Edgewood Arsenal experimented with BZ, along with LSD, THC, ketamine, opioids and other drugs on hundreds of military personnel and civilians into the mid-1970s. Originally designated 'TK', the chemical agent received the NATO designation BZ in 1961.

The characteristic that makes BZ and other glycolates an incapacitating rather than a toxic chemical warfare agent is its high safety ratio. The amount required to produce effects is a thousand or more times less than a fatal dose of the compound. Clinical effects from ingestion or inhalation of BZ appear after an asymptomatic or latent period that may be as little as 30 minutes or as long as 24 hours; the usual range is 30 minutes to 4 hours, with a mean of 2 hours. However, effects may not appear up to 36 hours after skin exposure to BZ.

Because BZ is odorless and nonirritating, and because clinical effects are not seen until after a latent period of 30 minutes to 24 hours, exposure could occur without the knowledge of casualties. The high-efficiency particulate air (HEPA) filter in the canister of the chemical protective mask prevents exposure of the face and respiratory tract to aerosolized BZ. The chemical protective ensemble protects the skin against contact with BZ or other incapacitating agents dispersed as fine solid particles or in solution. Protection against ingestion would depend upon a high index of suspicion for BZ-contaminated food or drink.

The National Institute for Occupational Safety and Health (NIOSH) reports that "QNB is an incapacitating agent and has been considered historically for use as a chemical warfare agent. A very potent drug, QNB causes confusion and hallucinations; it also affects circulation, digestion, salivation, sweating, and vision. Impairments caused by QNB are generally temporary and unlikely to be fatal; however, they can be severe if exposure is large enough.... QNB can be absorbed into the body by inhalation, ingestion, skin contact, or eye contact. Inhalation and ingestion are important routes of exposure for the solid. Skin and eye contact are routes of exposure when QNB is mixed with a liquid solvent that would enhance absorption.... Acetylcholine is a neurotransmitter (a chemical that transmits signals from one nerve to the next) in both the central and peripheral nervous systems. QNB works by blocking the acetylcholine receptor of the nerve on the “receiving end” of the signal. By this mechanism, QNB prevents the normal transmission of nerve signals in both the central and peripheral nervous systems. The resulting peripheral nervous system effects due to QNB exposure are known as the “anticholinergic toxidrome.”"

The chemical BZ, or 3-quinuclidinyl benzilate, also known as "agent buzz", was produced at Pine Bluff Arsenal between 1962 and 1965. It was dropped from the chemical arsenal because its effects on enemy front-line troops would be varied and unpredictable. BZ is usually disseminated as an aerosol with the primary route of entry into the body through the respiratory system; the secondary route is through the digestive tract. BZ blocks the action of acetylcholine in both the peripheral and central nervous systems. As such, it lessens the degree and extent of the transmission of impulses from one nerve fiber to another through their connecting synaptic junctions. Its pharmacological action is similar to that of other anticholinergic drugs (e.g., atropine, scopolamine, etc.), but longer lasting. It stimulates the action of noradrenaline (norepinephrine) in the brain, much as do amphetamines and cocaine. Thus, is may induce vivid hallucinations as it sedates the victim. Toxic delirium is very common.

Anticholinergic hallucinations differ from the often vague, ineffable, and often transcendent-appearing hallucinations induced by hallucinogenic indoles such as LSD. Hallucinations from BZ tend to be realistic, distinct, easily identifiable (often commonly encountered objects or persons), and panoramic, and they usually become less extreme during the course of the intoxication.

BZ is a glycolate anticholinergic compound dispersed as an aerosolized solid when intended for inhalation, or as agent dissolved in one or more solvents when intended for ingestion or percutaneous absorption. Acting as a competitive inhibitor of acetylcholine at postsynaptic and postjunctional muscarinic receptor sites, BZ causes peripheral nervous system (PNS) effects that in general are the opposite of those seen in nerve agent poisoning. Due to PNS effects, patients have been described as “dry as a bone, hot as a hare, red as a beet, and blind as a bat.” Central nervous system (CNS) effects include stupor, confusion, and confabulation with concrete and panoramic illusions and hallucinations, and with regression to automatic “phantom” behaviors such as plucking and disrobing. The combination of anticholinergic PNS and CNS effects aids in the diagnosis of patients exposed to these agents.

The patient is often disoriented to time and place. Disturbances in judgment and insight occur. The patient may abandon socially imposed restraints and resort to vulgar and inappropriate behavior. Perceptual clues may no longer be readily interpretable. The patient is easily distracted and may have memory loss, most notably short-term memory. In the face of these deficits, patients try to make sense of their environment and will not hesitate to make up answers on the spot to questions that confuse them. Speech becomes slurred and often senseless, and loss of inflection producesa flat, monotonous voice. References become concrete and semiautomatic, with colloquialisms, clichés, profanity, and perseveration.

Decreased cholinergic stimulation of pupillary sphincter muscles allows a-adrenergically innervated pupillary dilating muscles to act essentially unopposed, resulting in mydriasis. In fact, the cosmetic effect of mydriasis in women who applied extracts of deadly nightshade topically to their eyes explains the name “belladonna” [beautiful lady] given to this plant.

BZ is widely used in pharmacology as a muscarinic receptor marker. Anticholinergic hallucinogenic compounds are present in thorn apple as well as other plants of the family Solanaceae, which also includes black henbane (Hyoscyamus niger), belladonna (or deadly nightshade, Atropa belladonna), woody nightshade (Solanumdul camara), and Jerusalem cherry (Solanum pseudocapsicum). These plants contain varying proportions of the anticholinergic glycolates atropine, hyoscyamine, and hyoscine.

Although BZ figured prominently in the plot of the 1990 movie Jacob’s Ladder as the compound responsible for hallucinations and violent deaths in a fictitious American battalion in Vietnam, this agent never saw operational use. In February 1998, the British Ministry of Defence released an intelligence report that accused Iraq of having stockpiled large amounts of a glycolate anticholinergic incapacitating agent known as Agent 15. This compound is speculated either to be identical to BZ or a closely related derivative. Also in 1998, there were allegations that elements of the Yugoslav People’s Army used incapacitating agents that caused hallucinations and irrational behavior against fleeing Bosnian refugees. Physical evidence of BZ use in Bosnia remained elusive, however.

The US Army Chemical Corps weaponized BZ in 1962, mass producing the agent and packing it into the M44 smoke generator cluster and M43 BZ cluster bombs for use against squad or company-sized enemy forces. Between 1962 and 1988, 1,500 M44 and M43 rounds were produced, and stored at the Pine Bluff Arsenal in Jefferson County, Arkansas.

In 1988, the US began work on demilitarization of BZ stockpiles. As part of that work, a method was developed in collaboration between NIST and the US Army R&D laboratory at Fort Detrick, MD for purposes of monitoring workers. That method was based on GC/MS of the TMS derivatives, and monitored all three analytes (BZ, BA and Q). Detection limits were 0.5 ng/mL for BZ and 5 ng/mL for the hydrolysis products. The CDC developed and validated an LC/MS/MS method for the analysis of BZ and BA and a GC/MS method for Q to be used as validation. Detection limits are less than 1 ppb for each of the analytes.

The US Army conducted research on the effects of BZ in male volunteers [Ketchum JS. The Human Assessment of BZ. Human Investigations Facility, Directorate of Medical Research, U.S. Army Chemical Research and Development Laboratories; Edgewood Arsenal, MD; 1963. (CRDL Technical Memorandum 20–29)]. Severity of BZ-induced effects (criterion for incapacitation) was evaluated using a total response index (TRI). Maximal doses produced onset of stupor within 3 hours and performance decrement to zero within 4 hours followed by protracted sleepiness, disorganized behavior, continual hallucinations, possible outbursts of fear and anger, delirium, which subsided within 72 hours followed by a complete recovery by 120 hours. Effects observed at all exposures were reversed 7-days post-exposure with no medical intervention.

The ex-Russian spy Sergei Skripal and his Yulia daughter were found unconscious on 04 March 2018 on a bench at a shopping center in the UK city of Salisbury. A police officer, detective sergeant Nick Bailey, was inadvertently poisoned after tending to the Skripals, but was released from hospital on 22 March 2018, after more than two weeks treatment. Yulia S. Skripal was released from hospital on 10 April 2018, more than a month after the incident, at which time her father remained hospitized.

Russian claims that the chemical agent in the Skripal case was of American origin are implausible. It is well established that the effects of BZ wear off after a few days, while all three victims in this case were hospitalized for weeks. The effects of BZ are remarkable [stark raving mad, mad as a Hatter, barking mad, etc], and were not in evidence in this case.

Progaganda should not look like propaganda. To be effective, it must be convincing, an edifice of facts laced with strands of fiction. The Russian claims that the chemical agent in the Skripal case was BZ are unbelievable.