The reactivation of cholinesterase inhibited with organophosphorus compounds. 2. Reactivation by pyridinealdoxime methiodides.

Material8 The pyridinealdoxime methiodides were obtained by boiling the oximes with methyl iodide in ethanol (Green & Saville, 1956). Quinoline-4-aldoxime methiodide, m.p. 232-233° (Found: I 40x2. C11H11N20I requires 1 40.4%) and pyridine-2-alidoxime ethiodide, m.p. 186-188° (Found: I 45-3. C8H11N20I requires I 45-6%) were prepared similarly. Reactivation experiments These were carried out on human erythrocytes at 250 and pH 7*4 as described earlier (Davies & Green, 1956), whereby samples from a reactivation mixture containing inhibited enzyme and reactivator were taken at intervals and analysed for ChE activity by the electrometric method. With the higher concentrations of oxime, reactivation continued to an appreciable extent in the assay vessel despite the presence of excess (0.01 M) of acetylcholine, which gives the appearance of exceptionally rapid reactivation during the first few seconds of contact between the oxime and inhibited enzyme. For pyridine-2-aldoxime methiodide and ChE inhibited with tetraethylpyrophosphate (TEPP) or isopropyl methylphosphonofluoridate (Sarin) this effect is still noticeable even with a concentration of reactivator in the assay vessel of 10-5M. The effect can be readily compensated for if the extent of the apparent rapid reactivation is taken as the enzyme activity at zero time of contact between inhibited enzyme and reactivator. However, since this reduces the difference between the measured enzyme activities at zero and infinite time, the percentage error is increased and the calculated rates are less accurate.