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Effects of subacute pyridostigmine administration on mammalian skeletal muscle function
Author(s) -
Adler Michael,
Deshpande Sharad S.,
Foster Robert E.,
Maxwell Donald M.,
Albuquerque Edson X.
Publication year - 1992
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550120107
Subject(s) - pyridostigmine , pyridostigmine bromide , cholinesterase , atropine , stimulation , medicine , chemistry , endocrinology , acetylcholine , acetylcholinesterase , neuromuscular transmission , pharmacology , soman , diaphragm (acoustics) , anesthesia , myasthenia gravis , biochemistry , physics , acoustics , loudspeaker , enzyme
Abstract The subacute effects of pyridostigmine bromide were investigated on the contractile properties of rat extensor digitorum longus (EDL) and diaphragm muscles. The cholinesterase inhibitor was delivered via subcutaneously implanted osmotic minipumps (Alzet®) at 9 μg h −1 (low dose) or 60 μg h −1 (high dose). Animals receiving high‐dose pyridostigmine pumps exhibited marked alterations in muscle properties within the first day of exposure that persisted for the remaining 13 days. With 0.1 Hz stimulation, EDL twitch tensions of treated animals were elevated relative to control. Repetitive stimulation at frequencies >1 Hz led a use‐dependent depression in the amplitude of successive twitches during the train. Recovery from pyridostigmine was essentially complete by 1 day of withdrawal. Rats implanted with low‐dose pyridostigmine pumps showed little or no alteration of in vivo twitch tensions during the entire 14 days of treatment. Diaphragm and EDL muscles excised from pyridostigmine‐treated rats and tested in vitro showed no significant alterations in twitch and tetanic tensions and displayed the same sensitivity as muscles of control animals to subsequent pyridostigmine exposures. In the presence of atropine, subacutely administered pyridostigmine protected rats from two LD 50 doses of the irreversible cholinesterase inhibitor, soman. In the absence of atropine, the LD 50 of soman was not altered by subacute pyridostigmine treatment.