Basal Ganglia Dopamine-Gamma-Aminobutyric Acid-Acetylcholine Interaction inOrganophosphate-Induced Neurotoxicity

摘要

This annual report contains descriptions of investigations on: (1) prevention ofsoman toxicity after continuous administration of physostigmine and/or trihexphenidyl; and (2) effects of physostigmine and trihexyphenidyl (or scopolamine) treatment on the binding characteristics of muscarinic receptors. The effects of continuous infusion of guinea pigs with physostigmine salicylate and/or trihexyphenidyl on water consumption and body weights were examined as well as the effects of such infusions (as pretreatments) on soman-induced toxicity (as evidenced by tremors, convulsions, loss-of-righting reflex, hypothermia, and lethality). The results obtained clearly showed that subcutaneous infusion of the combination of physostigmine and trihexyphenidyl is less toxic to guinea pigs than is infusion with physostigmine alone. Furthermore, in terms of every symptom of soman toxicity which we noted, this combination pretreatment regimen was far superior to pretreatment with physostigmine alone, i.e., the incidence of toxicity signs was much lower (a higher percentage of animals was protected from soman-induced toxicity) and the latency to onset of toxicity signs was increased (allowing more time for employment of other supportive and antidotal measures that might be used to allay discomfort). (js)