The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC "Annex on Chemicals" some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman's assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.

• Keywords
• A-230, Acetylcholinesterase, Antidotes, Chemical Weapons Convention, Nerve agent surrogates,
• MeSH
• Acetylcholinesterase * metabolism   MeSH
• Antidotes pharmacology   MeSH
• Chemical Warfare Agents * toxicity   MeSH
• Cholinesterase Inhibitors * toxicity   MeSH
• Nerve Agents * toxicity   MeSH
• Organothiophosphorus Compounds toxicity   MeSH
• Oximes * pharmacology   MeSH
• Pralidoxime Compounds pharmacology   MeSH
• Pyridinium Compounds * pharmacology   MeSH
• Cholinesterase Reactivators * pharmacology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcholinesterase * MeSH
• Antidotes MeSH
• Chemical Warfare Agents * MeSH
• Cholinesterase Inhibitors * MeSH
• Nerve Agents * MeSH
• Organothiophosphorus Compounds MeSH
• Oximes * MeSH
• pralidoxime MeSH Browser
• Pralidoxime Compounds MeSH
• Pyridinium Compounds * MeSH
• Cholinesterase Reactivators * MeSH

This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer's disease, or as a warfare method due to the action of nerve agents. The chemical concepts related to the irreversible inhibition of AChE, its reactivation, and aging are discussed, along with a relationship to the current international legislation on chemical weapons.

• Keywords
• Alzheimer’s disease, Chemical Weapons Convention, acetylcholinesterase, nerve agents,
• MeSH
• Acetylcholinesterase * metabolism   MeSH
• Alzheimer Disease * drug therapy   enzymology   MeSH
• Chemical Warfare legislation & jurisprudence   MeSH
• Cholinesterase Inhibitors therapeutic use   MeSH
• GPI-Linked Proteins antagonists & inhibitors   metabolism   MeSH
• Humans MeSH
• Nerve Agents * MeSH
• Aging metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Acetylcholinesterase * MeSH
• ACHE protein, human MeSH Browser
• Cholinesterase Inhibitors MeSH
• GPI-Linked Proteins MeSH
• Nerve Agents * MeSH

"Novichoks" is the name given to the controversial chemical weapons supposedly developed in the former Soviet Union between the 1970s and the 1990s. Designed to be undetectable and untreatable, these chemicals became the most toxic of the nerve agents, being very attractive for both terrorist and chemical warfare purposes. However, very little information is available in the literature, and the Russian government did not acknowledge their development. The intent of this review is to provide the IJMS readers with a general overview on what is known about novichoks today. We briefly tell the story of the secret development of these agents, and discuss their synthesis, toxicity, physical-chemical properties, and possible ways of treatment and neutralization. In addition, we also wish to call the attention of the scientific community to the great risks still represented by nerve agents worldwide, and the need to keep constant investments in the development of antidotes and ways to protect against such deadly compounds.

• Keywords
• Novichoks, binary weapon, chemical warfare, nerve agents,
• MeSH
• Chemical Warfare * prevention & control   MeSH
• Chemical Warfare Agents chemical synthesis   chemistry   toxicity   MeSH
• Chemical Phenomena MeSH
• Decontamination MeSH
• Humans MeSH
• Nerve Agents chemical synthesis   chemistry   toxicity   MeSH
• Organophosphates chemical synthesis   chemistry   toxicity   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Chemical Warfare Agents MeSH
• Nerve Agents MeSH
• novichok MeSH Browser
• Organophosphates MeSH