Protection against the effects of anticholinesterases on the latencies of action potentials in mouse skeletal muscles.
1. Adult male albino mice were injected subcutaneously with an organophosphorous anticholinesterase to initiate excessive variability in the latency of indirectly elicited muscle action potentials (jitter) when assessed 5 days later. 2. Pretreatment of the mice with a single dose of pyridostigmine prevented the development of jitter after subsequent dosing with an organophosphate. 3. Treatment with one dose of pralidoxime (2PAM) prevented the development of jitter if given less than 1 h after treatment with ecothiopate, a reactivatable inhibitor of cholinesterase. Similar treatment with 2PAM after a non-reactivatable inhibitor did not prevent the development of jitter. The repeated administration of 2PAM over 12 h did ameliorate jitter. 4. Pretreatment of mice orally with alpha-tocopherol and N-acetylcysteine, known to prevent ecothiopate-induced myopathy, did not prevent the development of jitter after ecothiopate. 5. It is concluded that the development of jitter was a consequence of the inhibition of acetylcholinesterase, and although jitter did not develop acutely, the potential for the full development of jitter was achieved about 1 h after intoxication with ecothiopate. The development of jitter did not involve the generation of free radicals. Reduction of the early effects of intoxication with anticholinesterases by pyridostigmine or 2PAM prevented the development of jitter.
Kelly
S S
SS
Pharmacological Laboratories, Aston University, Birmingham.
Ferry
C B
CB
Bamforth
J P
JP
Das
S K
SK
D000110:Acetylcholinesterase / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D004594:Electrophysiology; D008297:Male; D051379:Mice; D008839:Microelectrodes; D009132:Muscles / Q000187:drug effects* / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D011220:Pralidoxime Compounds; D014810:Vitamin E; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide; C028797:pralidoxime; D000111:Acetylcysteine