1 The purpose of this investigation was to determine the long-term effects of a single dose of persistent anticholinesterases on muscle action potentials evoked by nerve stimulation. 2 Action potentials (APs), elicited by stimulation of the phrenic nerve, were recorded intracellularly in muscle fibres of mouse diaphragm. The time between stimulus and AP was measured and the variability of this latency was calculated during trains of APs. At the beginning of trains of APs there was an increase in latency, and this delay was also measured. 3 Within 3h of subcutaneous injection, a single dose (500nmolkg-1) of the anticholinesterase, ecothiopate produced about 90% reduction in the acetylcholinesterase activity of homogenates of mouse diaphragm muscle, but five days after injection, this activity was not different from values in untreated animals. The initial delay of APs and the variability of latencies were increased four fold and two fold respectively, remained at these maxima from the 1st to the 5th day after ecothiopate, and returned to the values in untreated animals between 15 and 27 days after ecothiopate. 4 These effects of ecothiopate on AP latency were dose-dependent and were also seen in extensor digitorum longus and soleus muscles. 5 Other anticholinesterases used were BOS (pinacolyl S-(2-trimethylaminoethyl)methylphosphonothioate), a quaternary compound, and diisopropyl fluorophosphate, a tertiary compound, which had effects similar to those of ecothiopate; the greater duration of the effects of this compound may be related to the greater duration of reduction in cholinesterase activity. 6 Ecothiopate had no effect on the delay or variability of latencies of endplate potentials which were recorded in cut-fibre preparations 5 days later. 7 It is concluded that the effects of ecothiopate on the latencies of indirectly-evoked muscle APs are postjunctional, may not be related to the degree of reduction in cholinesterase activity at the time of recording, and are not directly linked to necrosis.
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 a-tocopherol and N-acetylcysteine, known to prevent ecothiopateinduced 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.