Journal
ARCHIVES OF TOXICOLOGY
Volume 76, Issue 10, Pages 589-595Publisher
SPRINGER-VERLAG
DOI: 10.1007/s00204-002-0382-2
Keywords
nerve agents; acetylcholinesterase; erythrocytes; diaphragm; HI 6; oximes; reactivation
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The well-documented efficacy of HI 6 dichloride in reactivating acetylcholinesterase (ACNE) inhibited by nerve agents is curtailed by its poor water-solubility at temperatures below 10degreesC. This drawback can be circumvented by using HI 6 dimethanesulfonate, which has been developed in our laboratory. Since investigations on the efficacy of this new entity are lacking, it has been proposed that some bridging experiments be performed, aimed at demonstrating reactivator equivalence in vitro. The reactivating properties of the two salts were compared on human erythrocyte ACNE inhibited with paraoxon, sarin, cyclosarin and agent VX. The comparison was extended to cynomolgus erythrocytes exposed in vitro for satin and VX. Finally, mouse diaphragm preparations were circumfused with sarin, cyclosarin and VX and reactivation by each of the HI 6 salts was examined in muscle homogenates. ACNE activity in erythrocyte suspensions was monitored by a modified Ellman procedure, muscle ACNE by a radiometric assay. In all models tested no differences between the HI 6 salts could be detected (P=0.05). From these data, equipotency in ACNE reactivation by the two HI 6 salts can be anticipated.
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