Cholinesterase learning

As we soon learned, tetrahydro-aminoaeridine (THA) is less effeetive in some respeets than physostigmine in reversing seopolamine induced decrements in NF% scores (Fig. 67) but surprisingly, does seem to shorten the duration of belladonnoid intoxication. This may reflect a greater affinity for the cholinesterase enzyme. THA s tendency to cause temporaiy liver enzyme abnormalities, however, persuad us to avoid its further use. 

Scopolamine-induced impairment of learning and retention in the water maze was fully prevented by ondansetron when given in combination with a cholinesterase inhibitor, tacrine. Combined treatment with ondansetron and flumazenil was able to significantly increase ACh release in situations of cholinergic hypoactivity. 73, 110... 

Buccafusco, J.J., Heithold, D.L., Chon, S.H. (1990). Long-term behavioral and learning abnormalities produced by the irreversible cholinesterase inhibitor soman effect of a standard pretreatment regimen and clonidine. Toxicol. Lett. 52 319-29. 

Again, Dr Sim was the initial subject and received a 30-s injection of 0.225 xg kg-1 of VX which caused a decrease in erythrocyte cholinesterase activity to 63% of baseline. After 2 h, an intravenous infusion of 1 p.g min-1 was begun. A variety of minor effects occurred during the infusion, but at 3.5 h he became pale, stopped talking, appeared out of contact , and had profuse salivation and vomiting. The confu-sional state lasted about 15 min. It was learned later that his erythrocyte cholinesterase activity was 15% of his baseline, (Kimura et al., 1960). 

It. should also be noted that some studies have shown improvements in learning associated with exposure to cholinesterase inhibitors. These effects in rats were either transient during exposure or observed at low doses or after recovery the compounds studied include parathion (water maze Evens et al., 1998), chlorfenvinpho.s (active avoidance Socko et al., 1999), and aldicarb (passive avoidance and water maze Palumbo et al., 2001). These observations probably reflect the memory-enhancing properties of low levels of cholinergic stimulation, the basis for the therapeutic use of some cholinesterase inhibitors in the treatment of Alzheimer s dementia. 

At around the same time, a small circle of Nazi officials learned about the discovery of Soman, one of the most deadly nerve agents known to man, which stiU required further development. Unbeknown to Schrader and many others working in the chemical warfare field, Richard Kuhn, director of the Kaiser Wilhelm Institute for Medical Research in Heidelberg, and his team of scientists had been commissioned by the military to screen various organophosphorus compounds for their level of cholinesterase (ChE) inhibition, and had discovered Soman in the process. When inhaled. Soman turned out to be twice as toxic as Sarin, was able to penetrate through the skin, and quickly affected the central nervous system. Because it inhibited cholinesterase very rapidly, the effective use of antidotes such as atropine was considerably reduced. Experiments on dogs and apes at Gross laboratory in Elberfeld quickly established the enormous toxicity of the new substance. 

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