Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of pretreatment with both sub-paralyzing and paralyzing doses of pancuronium and d-tubocurarine, on the onset and duration of succinylcholine-induced neuromuscular blockade were evaluated and compared in 225 patients. D-tubocurarine antagonized both onset and duration of succinylcholine block, while pancuronium produced a dual effect, antagonizing the onset and potentiating the duration of succinylcholine block. Pretreatment with d-tubocurarine (0.07 mg/kg, 0.3 mg/kg and 0.6 mg/kg) increased the time to onset of succinylcholine paralysis from 28 to 118%, and decreased the duration from 16 to 37%. Pancuronium (0.02 mg/kg, 0.04 mg/kg and 0.08 mg/kg) also antagonized the onset of succinylcholine paralysis with increases of 32 to 114%, but potentiated its duration from 30 to 103% compared with succinylcholine alone in the same patients. Although pancuronium markedly inhibited serum cholinesterase in vitro (I50=5 X 10(-7) mol) there was only a 10% inhibition of cholinesterase in vivo after pancuronium 0.08 mg/kg.
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PMID:Dual action of pancuronium on succinylcholine block. 84 75

1. The inhibition by pancuronium of acetylcholinesterase (AChE) and of plasma cholinesterase (ChE) was investigated in vitro regarding a) the sensitivity of both enzymes; b) the mechanism and constants of inhibition; and c) the relationship between the neuromuscular blocking and the anticholinesterase activity of pancuronium. 2. Pancuronium is a reversible inhibitor of both AChE and ChE. The inhibitory potency regarding ChE ([I]50=2.7 X 10(-7) M; Ki=4.2 X 10(-8) M) is highly selective and about 1000-fold higher than compared to AChE ([I]50=2.4 X 10(-4) M; Ki=3.5 X 10(-5) M). 3. The kinetic analysis by means of an Lineweaver-Burk plot and an Arunlakshana-Schild plot displayed a pure competitive mechanism of inhibition. 4. The inhibition of AChE and ChE is thought to be induced by a reversible binding of pancuronium to the anionic subsite of the active center, thus decreasing the formation of the primary enzyme-substrate complex. 5. The clinical administration of pancuronium for muscular relaxation during anaesthesia (0.01-0.08 mg/kg) will result in a concentration of approximately 10(-7)=10(-6) M in the extracellular fluid. Thus, an inhibition of plasma ChE can be expected to occur under clinical conditions, however, probably without practical significance.
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PMID:[On the inhibition of cholinesterases by pancuronium (author's transl)]. 85 9

Pancuronium causes a powerful and highly selective inhibition of human serum cholinesterase in vitro. The inhibition was studied in serum from 14 individuals of both sexes (5-60 years of age) with normal reactions to suxamethonium. Pancuronium, in a concentration of 2.3 x 10(-7) M, caused a 50% inhibition of the enzymatic hydrolysis of acetylcholine, when this substrate was present in a concentration of 10 x 10(-3) M. The same I50 value was also found for a commercial preparation of human serum cholinesterase. The inhibition was reversible and competitive in type. Pancuronium inhibition of the acetylcholinesterase in human red blood cells and from the electric eel was more than one thousand times weaker. Thus pancuronium is one of the most selective inhibitors of serum cholinesterase described so far. The in vivo activity of the serum cholinesterase in four patients receiving pancuronium 0.1 mg/kg decreased, during the first 3 min, by 60-80%, from the pre-induction value. After this a slow recovery occurred with 40% depression remaining at 45 min after the injection. The tachycardia produced by pancuronium may be related to this selective inhibition of serum cholinesterase. It is suggested that relaxants which selectively inhibit serum cholinesterase also selectively block the cardiac muscarinic receptors.
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PMID:The inhibition of cholinesterases by pancuronium. 119 83

The adverse reactions seen following administration of neuromuscular blocking agents are mainly cardiovascular. Due to the lack of specificity for the nicotinic receptor at the neuromuscular junction, these agents may interact with receptors in autonomic ganglia and muscarinic receptors in the heart. Furthermore, muscle relaxants may have histamine-releasing properties. The cardiovascular effects vary with potency and specificity of the drug, depending mainly on the chemical structure. Pancuronium, fazadinium and especially gallamonium block cardiac muscarinic receptors, and tachycardia may be seen. Atracurium, metocurine and in particular d-tubocurarine have histamine-releasing properties and may cause flushing, hypotension and tachycardia. Vecuronium has no effect on the cardiovascular system. The effect of succinylcholine on heart rate differs between children, where bradycardia is seen, and adults in whom tachycardia may follow. However, bradycardia may occur in adults following a single dose. Succinylcholine increases plasma potassium, especially in patients with nerve damage, and arrhythmias may be observed. The neuromuscular adverse effects of succinylcholine, such as fasciculations and increased gastric and intraocular pressure, may be prevented by precurarisation. Many drugs interact with neuromuscular blocking agents and there is often a potentiation of the neuromuscular effect. This is of clinical importance in the case of antibiotics, inhalational anaesthetics, lithium and cyclosporin. Difficulty in reversing the block may occur with calcium channel blockers and polymyxin. However, some drugs, such as phenytoin, carbamazepine and lithium, may cause resistance to neuromuscular blocking agents. Furthermore, clinically important interactions exist between individual neuromuscular blocking drugs. Precurarisation with a non-depolarising drug prolongs the onset of succinylcholine, and conversely a prolonged effect of non-depolarising drugs is seen following succinylcholine. The effect of succinylcholine is markedly prolonged if the drug is administered during recovery from pancuronium blockade or following neostigmine for reversal. Succinylcholine is hydrolysed by plasma cholinesterase, and drugs which decrease the activity of this enzyme may produce a prolonged block, i.e. contraceptive pills, cyclophosphamide, echothiopate and organophosphate.
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PMID:Adverse reactions and interactions of the neuromuscular blocking drugs. 268 31

Pancuronium bromide, a 3,17-diacetoxy-5 alpha-androstane, and three of its analogues, the 17-desoxy, the 3,17-dibutyryloxy and the 16-N-monoquaternary ammonium derivatives have been used as inhibitors of the usual and atypical plasma cholinesterase variants. In all cases the usual enzyme is more sensitive to inhibition by the substituted steroids than the dibucaine resistant enzyme. The relative affinities of the bis-quaternary ammonium compounds for either enzyme is in the order dibutyryloxy derivative > 17-desoxy derivative greater than or equal to pancuronium bromide. The monoquaternary compound has the least affinity of all the inhibitors for the usual enzyme but the greater affinity for the atypical enzyme. These observations show that the bis-quaternary compounds are very powerful differentiators of the variants. The monoquaternary derivative shows less differential inhibition, but provides additional evidence that the usual and dibucaine resistant variants differ in structure at or near their esteratic active site.
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PMID:Inhibition of the plasma cholinesterase variants by pancuronium bromide and some of its analogues. 610 7

Electromyographic potentials of fasciculations were studied in ten patients with amyotrophic lateral sclerosis (ALS). The EMG recordings were made from the extensor digitorum brevis muscle. The EMG recording was so selective that only one motor unit potential appeared on maximal voluntary effort and on supramaximal electrical stimulation of the peroneal nerve. In a series of fasciculations, the shapes of the EMG potentials varied, while in a series of voluntary twitch activations of electrical nerve stimulations the EMG potentials were mainly constant. Fasciculations were followed by antidromic impulses in the test unit axon as judged from collision tests, and they persisted after lidocaine blockades of the nerve to the muscle. The findings are compatible with a conclusion of distal multifocal triggering of fasciculation. Fasciculating motor units had voluntary firing properties close to those of normal low-threshold motor units. Widespread fasciculations were abolished by a nonparalytic dose of a synthetic curare derivative (Pavulon) and augmented by administration of neostigmine in two cases. The fasciculations in ALS thus have the same characteristics as experimental fasciculations evoked by cholinesterase inhibitors, and there is reason to believe that the underlying pathophysiological mechanism is similar in the two cases.
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PMID:Pathophysiology of fasciculations in ALS as studied by electromyography of single motor units. 708 17

A steroid, the dibutyrate analogue of pancuronium bromide (9.8 X 10(-8)M), has been used as differential inhibitor in the study of the plasma cholinesterase variants. Pancuronium dibutyrate numbers have been measured for 190 individuals, and the mean values for six of the known genotypes, E1uE1u, E1uE1f, E1uE1a, E1fE1a, E1aE1a, and E1fE1f, have been calculated. Evidence is presented that a combination of the pancuronium dibutyrate number and the fluoride number give better resolution of the six genotypes than the combination of the pancuronium dibutyrate and the dibucaine number. This new differential inhibitor has real potential for revealing the probable existence of new genotypes.
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PMID:Differential inhibition of plasma cholinesterase variants using the dibutyrate analogue of pancuronium bromide. 728 15

Pancuronium bromide (PCBr) inhibition effect on enzyme cholinesterase from pooled human serum (Che, EC 3.1.1.8 acylcholine acylhydrolase) was used for development of a spectrophotometric kinetic method for PCBr determination in human serum and urine. Optimal conditions for the basic and inhibitor reactions were established: pH=7.7 and substrate concentration c(benzoylcholine chloride)=1.33 mmol/L. Kinetic parameters were also determined: Michaelis-Menten's constant K(M)=0.40 mmol/L, maximal reaction rate V(max)=52.2 micromol/L min, inhibition constant K(i)=0,56 micromol/L and IC(50)=1.31 micromol/L. Linear dependence between the reaction rate and inhibitor concentration exists in PCBr concentration range 8.20-68.25 nmol/L, which corresponds to the real sample concentrations from 0.328 to 2.730 micromol/L. The method detection and quantification limits were 2.01 nmol/L and 6.67 nmol/L, respectively. Precision of the method was tested for three pancuronium concentrations (10.70, 29.35 and 51.25 nmol/L). Relative standard deviation (RSD) was in the range 0.15-7.45%. Accuracy was examined by standard addition method. Influence of the substances usually present in serum and urine on the reaction rate was tested. The developed method was applied for PCBr content determination in serum model samples, urine model samples and in urine taken during surgery. The method has good sensitivity, accuracy, precision and it is suitable for clinical practice.
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PMID:Cholinesterase inhibition based determination of pancuronium bromide in biological samples. 1680 73