The Effects of Organophosphorus Anticholinesterase Compounds on Brain Glucose and Energy Metabolism.
Annual summary rept. 1 Oct 81-30 Sep 82,
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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The purpose of these experiments was to determine the effect of an organophosphorus cholinesterase inhibitor, paraoxon, on glucose utilization and the levels of intermediary metabolites in brain. The 24 hr. I.V. LD50 of paraoxon in rats was 0.764 or - 0.032 micromolkg. A dose of 0.8 of the LD50 did not result in any evidence of hypoxia in rats up to 2 hr. post-injection. The levels of glucose, pyruvate, glutamate, lactate, ATP, and phosphocreatine were determined in the following brain areas cortex, midbrain, thalamus-basal ganglia, cerebellum and brain stem at 2, 10, 32 or 128 min. after administration of 0.8 or 0.5 of the LD50 of paraoxon. The only consistent change observed was an elevation of tissue glucose. Injection of 0.8 of the LD50 of paraoxon resulted in a significant depression in glucose utilization in the cortex for up to 30 min. However this decrease was not observed at 128 min. when the peripheral cholinergic effects were also absent. The diminished glucose utilization may be the cause of the increase in brain glucose observed. The decrease in glucose utilization may be due to an increase in inhibitory cholinergic neuronal activity.