Effects of subacute pyridostigmine administration on mammalian skeletal muscle function.
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 micrograms h-1 (low dose) or 60 micrograms 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 greater than 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 LD50 doses of the irreversible cholinesterase inhibitor, soman. In the absence of atropine, the LD50 of soman was not altered by subacute pyridostigmine treatment.
Adler
M
M
Neurotoxicology Branche, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010.
Deshpande
S S
SS
Foster
R E
RE
Maxwell
D M
DM
Albuquerque
E X
EX
D000110:Acetylcholinesterase / Q000097:blood; D000222:Adaptation, Physiological; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003864:Depression, Chemical; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007260:Infusion Pumps; D007928:Lethal Dose 50; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000187:drug effects* / Q000502:physiology; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D012999:Soman; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide