The huge number of OP poisoning cases and the big stocks of still available nerve agents in diverse countries make necessary the discovery of large OP broad-spectrum antidotes. Occasionally, there is the occurrence of terrorist attacks, such as that in Syria, in 2013, where Sarin terribly affected the civilians. There are some indications that about 3 million cases of OP poisoning occur in the world each year. This is an important step in continuing this remarkable research so that new studies can begin. This review will allow us to evaluate the major advances made in the discovery of new acetylcholinesterase reactivators by reviewing all patents published between 20. In addition, the discovery of ways to restore AChE in the aged form is also of great importance. These researches have been moving farther into the search for novel agents that possess better effectiveness of reactivation and broad-spectrum reactivation against diverse OP agents. Over the past years, researchers worldwide have made efforts to identify and develop novel active molecules. This review was developed with the purpose of covering the new advances in AChE reactivation. Within the most outstanding reactivators, the substances denominated oximes stand out, showing good performance for reactivating AChE and restoring the normal synaptic acetylcholine (ACh) levels. To combat the toxic effects of some AChEI, such as organophosphorus (OP) nerve agents, many compounds with reactivator effects have been developed. Irreversible or prolonged inhibition of AChE, therefore, elevates synaptic ACh leading to serious central and peripheral adverse effects which fall under the cholinergic syndrome spectra. Acetylcholinesterase (AChE) is the key enzyme responsible for deactivating the ACh neurotransmitter.
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