Neuromuscular function in fluostigmine intoxication

In experiments with isolated nerve-diaphragm preparation and intact anterior tibial muscle of the rat, it was found that repeated administration of fluostigmine (1 to 30 days) caused a decrease of the indirectly elicited tetanic response and post-tetanic depression of twitch response. Impairment of neuromuscular transmission increased during the first days of treatment. In the following period marked recovery occurred in spite of further fluostigmine administration. The recovery of neuromuscular function was much more pronounced in diaphragm preparation than in the anterior tibial muscle. It was not associated with any recovery in the activity of inhibited acetylcholinesterase. The sensitivity of the neuromuscular junction to carbachol increased during the first days of treatment and then decreased in the later stage. The sensitivity to d-tubocurarine in the diaphragm preparation decreased on the tenth day of treatment and returned to normal value after 30 days. In the anterior tibial muscle the sensitivity to d-tubocurarine slightly decreased on the fifth day, and after 20 to 30 days, was markedly increased. The underlying mechanisms are discussed.