ABSTRACT
Anticholinesterases are agents that inhibit the enzyme acetylcholinesterase (AChE) and other cholinesterases that degrade acetylcholine (ACh). The first known anticholinesterase agent was Calabar bean, known as “ordeal poison” or “ordeal bean”; its active ingredient is the carbamate compound physostigmine (Koelle 1975). It is thought that the Calabar bean was used by native tribesmen of Western Africa who used it in witchcraft rituals. The principle behind its use was that if a tribal member was accused of a capital crime, he or she would be subjected to a trial by ordeal in which they were forced to eat Calabar beans. If a person was innocent, he or she would quickly eat the beans with little apprehension, which would quickly induce
5.1 Introduction ................................................................................................. 135 5.1.1 Anticholinesterases as Chemical Warfare Agents ........................... 135 5.1.2 Physiology of Acetylcholine ............................................................ 137 5.1.3 Classification of Acetylcholinesterases ............................................ 138 5.1.4 Acute Toxicity of Organophosphate Chemical Threat Agents ........ 139 5.1.5 Acute Treatment Following Organophosphate Chemical Threat
Agent Exposure ................................................................................ 140 5.1.6 Delayed Neuropathology of Organophosphate Chemical Threat
Agents .............................................................................................. 141 5.2 Multiple Pathways Leading to Neuronal Degeneration .............................. 144
5.2.1 Activation of Caspases (Cysteine Requiring Aspartate Proteases) ......................................................................................... 146
5.2.2 Activation of Calpain (Calcium-Dependent Neutral Protease) ........ 147 5.3 Conclusions ................................................................................................. 151 5.4 Research Recommendations ....................................................................... 151 Acknowledgment ................................................................................................... 153 References .............................................................................................................. 153
vomiting and prevent death. On the other hand, if the person felt guilty and apprehensive, he or she might ingest the beans more slowly and obtain a lethal dose in the absence of vomiting. In 1864, an extract and elixir of Calabar bean was used medicinally, when it was named eserine; the structure was determined in 1925 and synthesized in 1935 (Koelle 1975). Although they are used as insecticides, carbamates also are utilized medicinally in the treatment of glaucoma and myasthenia gravis and include pyridostigmine bromide, ambenonium, neostigmine, and physostigmine (Koelle 1975).
