Structure-activity relationships in reactivators of organophosphorus-inhibited acetylcholinesterase. V. Quaternary salts of hydroxyiminomethylimidazoles.
The methiodides of (E)-1-methyl-2-hydroxyiminomethylimidazole, (E)-1-benzyl-2-hydroxyiminomethylimidazole, and (Z)-1-methyl-5-hydroxyiminomethylimidazole were tested in vitro as reactivators of phosphorylated acetylcholinesterase. From the hydrolysis rate measurements, it was ascertained that only the compounds derived from 2-hydroxyiminomethylimidazole had an activity comparable with that of methiodide of 2-hydroxyiminomethylpyridine, whereas the methiodide of (Z)-1-methyl-5-hydroxyiminomethylimidazole was inactive. The structure-activity relationships of these reactivators are briefly discussed.
Pyridinium, imidazolium and quinuclidinium compounds: toxicity and antidotal effects against the nerve agents Tabun and Soman.
This paper discusses the toxicity and antidotal effects of 32 compounds. Screening studies have shown that these compounds combined with atropine are effective antidotes against the organophosphate nerve agents Tabun and/or Soman, having a therapeutic factor equal or greater than 2.0 when tested in mice or rats. We analysed the results of these studies, and recommend that these compounds should be studied in more detail simultaneously with conventional antidotes (PAM-2, HI-6, Toxogonin, TMB-4) in order to assess whether they could broaden the choice of compounds now available for the treatment of organophosphate poisoning.
Comparison of Binaural Release from Forward Masking in Animals and Humans. Electrophysiological Studies
Evoked potentials in the inferior colliculus and auditory areas of the cortex were studied in anesthetized guinea pigs and long-latency auditory evoked potentials (LAEP) were studied in waking humans using sequential binaural presentation of pairs of clicks – the masker and the masked signal – with a variable interval between them, to provide the conditions needed for the psychophysical phenomenon of direct forward masking. Introduction of phase differences between the masker and the masked signal led to decreases in suppression of responses to the masked signal and to faster recovery of the reaction types recorded. The greatest relative differences between response magnitudes to antiphase and synphase masked signals were seen at the beginning of the recovery process, and were 1.6, 1.5, and 1.4 respectively for responses from the inferior colliculus, auditory area of the cortex, and LAEP at stimulus intensities of 50–65 dB sound pressure level, differences subsequently decreasing to zero. There was a positive correlation between this measure and the stimulus intensity. The greatest differences between the time at which the recovery process ended for responses to antiphase and synphase masked signals were 4, 250, and about 2000 msec respectively for the inferior colliculus, auditory area of the cortex, and LAEP.