The Effect of Edrophonium on Erythrocyte Acetylcholinesterase and Neuromuscular Function in the Rat

Barber, H E; Calvey, T. N.; Muir, Keith T.; Taylor, K.

doi:10.1111/j.1476-5381.1976.tb06963.x

Cited by 11 publications

(8 citation statements)

References 11 publications

(25 reference statements)

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“…In recent experiments in the rat, we have used a radiometrie enzyme assay to confirm the presence of this association. 3 Although edrophonium is metabolized by the liver to a 3-oxy-glucuronide,1 this conjugate has little or no biologie action, since the relation between acetylcholinesterase activity and the plasma concentration of edrophonium is identical in in vitro and in vivo conditions. 3 In consequence, enzyme inhibition bears a specific relationship to the concentration of the unchanged drug.…”

mentioning

confidence: 99%

“…3 Although edrophonium is metabolized by the liver to a 3-oxy-glucuronide,1 this conjugate has little or no biologie action, since the relation between acetylcholinesterase activity and the plasma concentration of edrophonium is identical in in vitro and in vivo conditions. 3 In consequence, enzyme inhibition bears a specific relationship to the concentration of the unchanged drug. In our experiments, the relation between the concentration of edrophonium in plasma and red cell acetylcholinesterase activity has been used to assess the clearance of the drug for 60 min after its intravenous administration in man.…”

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confidence: 99%

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Plasma concentration of edrophonium in man

Calvey

Williams

Muir

et al. 1976

Clin Pharma and Therapeutics

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The plasma concentration of edrophonium was measured in man after intravenous administration. In 5 patients, the clearance of edrophonium from the circulation during the 1-hr period of sampling was invariably resolved into 2 exponential components. An initial rapid phase of elimination from plasma (T/2 = 0.54 TO 1.92 Min) was followed by a much slower decline (T/2 = 24.23 to 45.00 Min), corresponding to the fall in concentration between 10 and 60 min. In parallel experiments in the rat, the clearance of 14C-edrophonium was resolved into 3 exponential components, although the final component could not be reliably defined until 1 to 3 hr after intravenous injection. It is suggested that the rapid fall in the plasma concentration of edrophonium in both species is not dependent on metabolism or excretion, but is due to the rapid uptake of the drug by the liver and kidneys.

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confidence: 99%

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confidence: 99%

Plasma concentration of edrophonium in man

Calvey

Williams

Muir

et al. 1976

Clin Pharma and Therapeutics

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“…The data preceding the peak of the secondary facilitatory phase were not included in the statistical analy- sis as this primary facilitation and subsequent decline has been shown to be quite unrelated to the plasma concentration of drug (Barber et al, 1976).…”

Section: Time Course Of the Inhibition Of Acetylcholinesterasementioning

confidence: 99%

“…Plasma was obtained from part of each sample by centrifugation and the plasma concentration of each drug was determined. The remainder of the blood sample was used for the determination of acetylcholinesterase activity in red cells as described by Barber et al (1976). Thus the design allowed the simultaneous monitoring of plasma concentration, acetylcholinesterase inhibition and muscle twitch tension throughout the experiments.…”

Section: Introductionmentioning

confidence: 99%

The Relationship Between the Pharmacokinetics, Cholinesterase Inhibition and Facilitation of Twitch Tension of the Quaternary Ammonium Anticholinesterase Drugs, Neostigmine, Pyridostigmine, Edrophonium and 3‐hydroxyphenyltrimethylammonium

Barber

Calvey

Muir

1979

British J Pharmacology

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1 The relationship between the concentration of drug in plasma, the inhibition of erythrocyte acetylcholinesterase and the facilitation of neuromuscular transmission has been studied in the rat after the administration of neostigmine, pyridostigmine, edrophonium and 3-hydroxyphenyltrimethylammonium (3-OH PTMA). 2 After the administration of neostigmine or pyridostigmine, acetylcholinesterase activity recovered only slowly due to the covalent nature of the inhibition. In contrast, recovery from the reversible inhibition caused by edrophonium or 3-OH PTMA was rapid and showed a direct relationship to the plasma concentration of these drugs. 3 There was a statistically significant linear correlation between the logarithm of the plasma concentration of the drugs and the increase in the tibialis twitch tension. 4 The relationship between the inhibition of acetylcholinesterase and the facilitation of neuromuscular transmission was complex. When the enzyme was less than 85% inhibited no facilitation occurred.Between 85% and 98% inhibition, facilitation was linearly related to enzyme inhibition. Above 98% inhibition, facilitation was unrelated to inhibition of the enzyme.

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“…This indicates that there is not a simple relationship between anticholinesterase action and alteration of muscle function. Barber, Calvey, Muir & Taylor (1975) also reported no correlation between the potentiation of the tibialis twitch tension and the plasma concentration of edrophonium or the inhibition of erythrocyte AChE. In order to study this aspect further, the relationship between inhibition of endplate AChE and alteration of muscle function should be studied on an isolated preparation rather than a muscle homogenate.…”

Section: Compoundmentioning

confidence: 99%

Effects of Certain Muscarinic Antagonists on the Actions of Anticholinesterases on Cat Skeletal Muscle

Brimblecombe¹,

French²,

Webb

1979

British J Pharmacology

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I The effects of some muscarinic antagonists, namely, N-ethyl-2-pyrrolidylmethyl-cyclopentylphenyl glycollate (PMCG), N-methyl-4-piperidyl-phenylcyclohexyl glycollate (PPCG, racemate and R and S enantiomers) and 4'-N-methyl-piperidyl-1-phenyl-cyclopentane carboxylate (G3063) on organophosphate (sarin, soman)-and carbamate (neostigmine)-induced twitch augmentation have been studied in cat soleus muscle. 2 The results of a preliminary study comparing the potency of sarin and soman in inhibiting the acetylcholinesterase activity of muscle in relation to the effect on the maximal twitch response indicated that there is not a simple relationship between degree of enzyme inhibition by these drugs and alteration of muscle function.3 The muscarinic antagonists studied were capable of preventing or reversing sarin-, soman-or neostigmine-induced twitch augmentation. Doses sufficient to give complete protection from the effects of the anticholinesterase agents had little or no effect on the twitch response of normal muscle. 4 The protective action of these muscarinic antagonists is dose-dependent but independent of known antagonist actions at muscarinic receptors. 5 The effects of some local anaesthetics (lignocaine, prilocaine, cinchocaine, procaine) and other membrane stabilizers (quinine, ketamine, chlorpromazine, triflupromazine) were compared with those of the muscarinic antagonists in an attempt to elucidate the mode of action of these acetylcholine antagonists. The evidence is insufficient to exclude the involvement of a membrane stabilizing action.

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The Effect of Edrophonium on Erythrocyte Acetylcholinesterase and Neuromuscular Function in the Rat

Cited by 11 publications

References 11 publications

Plasma concentration of edrophonium in man

Plasma concentration of edrophonium in man

The Relationship Between the Pharmacokinetics, Cholinesterase Inhibition and Facilitation of Twitch Tension of the Quaternary Ammonium Anticholinesterase Drugs, Neostigmine, Pyridostigmine, Edrophonium and 3‐hydroxyphenyltrimethylammonium

Effects of Certain Muscarinic Antagonists on the Actions of Anticholinesterases on Cat Skeletal Muscle

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