Abstract

The reactivators of acetylcholinesterase are very important components in the treatment of intoxications caused by organophosphate inhibitors such as tabun, sarin, soman, VX etc. and insecticides like echothiofat, metrifonat, chlorpyrifos etc. These inhibitors covalently bind on active site of mentioned enzyme and irreversibly inhibit its activity. The reactivator breaks the inhibitor-enzyme covalent bond and restores its activity. Unfortunately, there is no reactivator applicable for every type of inhibition; it means that every structural change in the molecule of inhibitor needs a specific structure of the reactivator. Therefore, development of more active acetylcholinesterase reactivators with broader spectrum is a major challenge actual from the point of view of war operations, accidents or terroristic attacks. Synthetic approaches, biological activity evaluation and structure-activity relationship studies of newly prepared acetylcholinesterase reactivators from 1990 to 2004 are summarized. Synthetic procedures used and the evaluation of antidotal efficacies are mentioned for individual types of reactivators. The main attention was paid to reactivators derived from pyridine carbaldoxime and imidazole carbaldoxime.

Keywords: organophosphate inhibitors (OPI), bispyridinium compounds, Pralidoxime, tabun-inhibited AChE, imidazole derivatives