Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An attempt was made to inhibit acetylcholinesterase activity in homogenates of rat brain and in 2% solutions of hemolyzed human or rat erythrocytes, with concentrations of acetylsalicylic acid/salicylic acid (ASA/SA) equivalent to those evident in human plasma 0--2 h after ingestion of 0.65 g of ASA. None of the 5 different ASA/SA mixtures used produced inhibition in any of the enzyme preparations while the reference compound, eserine, inhibited all. These results suggest that ingestion of ASA, at least in recommended doses, should not significantly influence acetylcholinesterase activity in vivo.
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PMID:The effect of acetylsalicylic acid/salicylic acid mixtures on acetylcholinesterase activity in vitro. 58 77

Preliminary disposition studies of the investigational, long-acting muscle relaxant doxacurium chloride (Nuromax) have demonstrated dual elimination by renal and hepatobiliary pathways, as well as slow hydrolysis by plasma cholinesterase. The present study compares the kinetics and dynamics of doxacurium in eight ASA physical status I or II elderly patients (67-72 yr of age) and eight ASA I or II young patients (22-49 yr of age). After institutionally approved written informed consent, kinetic and dynamic measurements were made after a 25-micrograms/kg bolus injection of doxacurium during 1.25 MAC nitrous oxide/oxygen/isoflurane anesthesia. Maximum twitch depression was similar in older patients (96.4% +/- 1.3%) to that in the young patients (96.6% +/- 1.8%). The time to achieve this level of block was significantly longer in the elderly than in the young (11.2 +/- 1.1 min versus 7.7 +/- 1.0 min, respectively). Recovery times to twitch heights of 5% and 25% of control tended to be prolonged and were more variable in the elderly (82.6 +/- 17.2 and 97.1 +/- 20.1 min, respectively) than in the young (54.8 +/- 9 and 67.5 +/- 8.2 min, respectively). Elimination half-life (96 +/- 20 min) and clearance (2.47 +/- 0.69 mL.kg-1.min-1) in the elderly patients were not statistically different from values found in the younger group. Volume of distribution at steady state in the elderly (220 +/- 80.2 mL/kg) was significantly larger than in the young (150 +/- 40.0 mL/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and pharmacodynamics of doxacurium in young and elderly patients during isoflurane anesthesia. 214 83

The present investigation reports the effect of chronic oral administration of mancozeb, a fungicide, on hepatic microsomal carboxylesterases/amidases or B-esterases responsible for hydrolytic metabolism of aspirin (acetylsalicylic acid or ASA) at pH 5.5 and 7.4, 2-acetylaminofluorene (AAF), acetanilide and p-nitrophenylacetate (NPA) and cholinesterase in rat. Oral administration of mancozeb (250 mg/kg/day) for 30 days caused significant stimulation of ASA esterase I (pH 5.5), ASA esterase II (pH 7.4), AAF N-deacetylase and acetanilide N-deacetylase in liver. However, the activities of NPA esterase and cholinesterase remained unaffected. Evaluation of induction kinetics demonstrated that the pattern and magnitude of responses of these microsomal hydrolases to mancozeb treatment for 7 days were comparable to those obtained after treatment for 30 days. The activities of hydrolases were not altered in animals killed 4 hr after an oral dose of mancozeb. Mancozeb did not affect these hydrolases in vitro.
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PMID:Effect of mancozeb on hydrolytic metabolism of xenobiotics. 227 66

Mivacurium chloride (BW B1090U), a bis-benzylisoquinolinium diester compound, was found to undergo hydrolysis in vitro by purified human plasma cholinesterase in a pH-stat titrator at 88% of the rate of succinylcholine at pH 7.4, 37 degrees C and 5 microM substrate concentration. In 72 consenting ASA Physical Status I-II patients receiving nitrous oxide/oxygen-narcotic-thiopental anesthesia, the neuromuscular blocking effect of mivacurium was assessed following bolus doses from 0.03 to 0.30 mg/kg, as well as during and following continuous infusions from 35 to 324 min in length. The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.08 mg/kg. At 0.1 mg/kg, 96% block developed, onset to maximum block required 3.8 +/- 0.5 min, and recovery to 95% twitch height occurred 24.5 +/- 1.6 (SE) min after injection. At 0.25 mg/kg, onset was 2.3 +/- 0.3 min; 95% recovery developed within 30.4 +/- 2.2 min, an increase in duration of action of only 24% versus 150% higher dosage. Comparative recovery indices from 5 to 95% or from 25 to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.3 mg/kg (range 12.9 to 14.7 and 6.6 to 7.2 min, respectively). In 38 patients who received mivacurium by continuous infusion (duration 88.1 +/- 7.1/47.1 min, SE/SD) for maintenance of 95 +/- 4% twitch inhibition, the mean 5-95% and 25-75% recovery indices after discontinuation of infusion were 14.4 +/- 0.6 and 6.5 +/- 0.3 min (P greater than 0.5 vs. all single bolus doses). The train-of-four (T4) ratio, within 2.6 +/- 0.5 min after 95% twitch recovery following bolus doses, averaged 79.5 +/- 1.8% (n = 32). Similarly, after discontinuation of infusions, the T4 ratio reached 73.4 +/- 1.9% within 3.4 +/- 1.9 min after 95% twitch recovery (n = 33). Antagonism of residual block was seldom indicated, but, to test ease of reversal, eight patients electively received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at 67 to 93 (76.6 +/- 3.5) % block. Twitch returned to 95% of control within 4.5 to 9.5 (6.3 +/- 0.5) min after neostigmine. Mivacurium may offer increased versatility in providing clinical muscle relaxation in a variety of situations. Further studies seem appropriate.
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PMID:The clinical neuromuscular pharmacology of mivacurium chloride (BW B1090U). A short-acting nondepolarizing ester neuromuscular blocking drug. 296 39

Doxacurium chloride (BW A938U) is a bis-quaternary benzylisoquinolinium diester nondepolarizing neuromuscular blocking compound that is minimally hydrolyzed by human plasma cholinesterase. The effect of bolus doses of doxacurium ranging from 10 to 80 micrograms/kg were studied in 81 consenting ASA physical status I and II patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental. The neuromuscular and cardiovascular effects of doxacurium were compared with those of eight patients receiving 100 micrograms/kg of pancuronium receiving identical anesthesia. The calculated ED95 for evoked twitch inhibition of the adductor pollicis at 0.15 Hz was 30 micrograms/kg. At 1.3 times the ED95 dose of doxacurium, recovery times to 5% and 25% of control twitch height were 59.2 +/- 4.1 (n = 23 of 26) and 75.7 +/- 5.6 (n = 23 of 26) min respectively. For pancuronium comparable recovery times were 81.7 +/- 10.3 (n = 8 of 8) and 83.0 +/- 8.4 (n = 5 of 8) min. Residual doxacurium blockade was readily antagonized by neostigmine. No dose-related effect on heart rate or mean arterial pressure was seen with doxacurium at doses up to and including 2.7 times the ED95 (80 micrograms/kg). Doxacurium administration did not result in any elevation of plasma histamine at doses up to and including 2.7 times the ED95. In this study doxacurium appears to be a long-acting nondepolarizing relaxant with readily reversible neuromuscular blocking effects and devoid of cardiovascular effects. This profile offers clinical advantages over current long-acting agents and further clinical trials seem appropriate.
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PMID:Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant. 297 33

Blood samples were drawn from 10 ASA physical status 1 and 2 patients before (baseline) and after the administration of cimetidine to determine the in vivo effect of cimetidine on plasma cholinesterase (PCHE) activity. The in vitro effects of cimetidine at different plasma concentrations were also studied using the same blood samples. PCHE activity in the baseline samples was 432 +/- 4.6 (mean +/- SEM) U/ml, the dibucaine number 82. Administration of oral cimetidine (300 mg) the night before and 2 hours before surgery, failed to have any effect on PCHE activity (no in vivo effect). Plasma cholinesterase activity in the presence of cimetidine in vitro at plasma concentrations of 1.5, 15, 150, and 1500 micrograms/ml was 428, 420, 397, and 177 U/ml, respectively. Thus, in vitro data showed that cimetidine at plasma concentrations (1.5 to 15 micrograms/ml) achieved with clinical doses also has no effect on PCHE activity.
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PMID:Cimetidine does not affect plasma cholinesterase activity. 333 48

The in vitro effect of procainamide on plasma cholinesterase (PCHE) activity in the plasma of ten normal ASA physical status I patients was studied using a kinetic method. The mean plasma cholinesterase activity without procainamide (control) was 0.90 +/- 0.09 units.ml-1. The dibucaine numbers of all the samples were in the normal range of 78 to 86, indicating normal genotypes. The mean plasma cholinesterase activity, in the presence of procainamide in concentrations of 5.0, 10.0, 20.0 and 40.0 micrograms.ml-1, was reduced to 0.73 +/- 0.04, 0.61 +/- 0.03, 0.45 +/- 0.02, and 0.36 +/- 0.01 units.ml-1, respectively. At therapeutic concentrations of 4 to 12 micrograms.ml-1, procainamide inhibited cholinesterase activity 15 to 30 per cent. The authors also showed that the concentration of procainamide required to inhibit 50 per cent of plasma cholinesterase activity was 20 micrograms.ml-1 (I50). The authors conclude that procainamide when tested in vitro had a statistically significant depressant effect on plasma cholinesterase activity at all the concentrations studied.
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PMID:The effect of procainamide on plasma cholinesterase activity. 367 82

In normal whole human blood in vitro, the source of the enzyme controlling the hydrolysis of aspirin (ASA) was found to be the erythrocyte (RBC). Experiments were carried out to determine whether this enzyme was membrane-bound or free in the lysate. The mean rates of ASA hydrolysis in comparable concentrations of intact RBC (1.61 +/- 0.20 mumole/liter/minute, n = 12 and 1.23 +/- 01.7 mumole/liter/minute, n = 5) were much faster than that measured in isolated RBC membranes (0.23 +/- 0.08 mumole/liter/minute, n = 6, P = less than 0.001). Detailed study showed that the RBC-related ASA esterase is located intracellularly and is not related to membrane acetylcholinesterase. The ASA esterase from crude lysate was purified 900-fold by means of DEAE Sephacel chromatography of active enzyme recovered from a 50% saturated ammonium sulfate fraction. Non-SDS polyacrylamide gel electrophoresis (pH 8.3 and 9.0) resulted in one major band and one or more small minor protein bands. When esterase activity was assayed in a non-stained gel, ASA depletion and salicylate production corresponded exactly to the major stained band. This band was eluted from another unstained gel, concentrated, and applied to an SDS gel. This yielded a single band with a molecular weight of approximately 95,000. The partially purified enzyme had a mean Km of 66.6 +/- 3.5 microM and a mean Vmax of 4.0 +/- 0.9 mumole/liter/minute/mg under the assay conditions. The results of inhibition studies suggested that this enzyme's activity is sulfhydryl group dependent, does not require divalent cations for activity, and is different from the RBC type D "nonspecific" esterases.
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PMID:Identification and partial purification of the major aspirin hydrolyzing enzyme in human blood. 683 77

To study the effect of decreasing the concentration of enflurane on a combined enflurane-d-tubocurarine (dTC) neuromuscular blockade, six ASA class I or II patients were studied using a continuous infusion of dTC and a sequence of decreasing end-tidal concentrations of enflurane. A constant infusion of dTC and a 2.2 per cent end-tidal concentration of enflurane decreased twitch tension to 8 per cent of control. Maintaining this same infusion rate of dTC, but decreasing the end-tidal concentration of enflurane to 1.35 and 0.5 per cent, increased the twitch tension to 57 and 91 per cent of control, respectively. The authors conclude that the enflurane contribution to muscle relaxation dissipates in a dose-dependent manner as the end-tidal concentration of enflurane is reduced. This factor may provide additional safety for patients because the anesthetic produces a component of relaxation that is readily reversible with time without the use of acetylcholinesterase inhibitors.
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PMID:Decreasing enflurane concentrations and d-tubocurarine neuromuscular blockade. 705 28

This study was designed to compare the effectiveness of antagonism of mivacurium blockade with either neostigmine, edrophonium, or spontaneous recovery. Thirty ASA physical status I or II patients provided informed consent and were randomized to one of the following groups: Group 1, placebo saline; Group 2, edrophonium (1 mg/kg); and Group 3, neostigmine (70 micrograms/kg) (n = 10/group). All studied patients had anesthesia induced with propofol and maintained with propofol/N2O/fentanyl. Mivacurium bolus of 0.2 mg/kg was used for endotracheal intubation and an infusion titrated to maintain deep levels of block (T1% = 1%-5%) (T1% = first response/control response x 100). The antagonist was injected at a deep level of the block (T1% = 1%-8%) and neuromuscular (NM) recovery was evaluated by train-of-four twitches (TOF). T1% was used during maintenance, whereas both T1% and TOF% (fourth response/first response x 100) were used during recovery. Investigators were blinded to the antagonist used. Plasma cholinesterase activity was measured prior to antagonist administration (0 min), as well as 15, 30, and 60 min after. Plasma cholinesterase activity was decreased to 29% of control at 15 min and remained at approximately 60% of the control after neostigmine administration. Edrophonium did not affect plasma cholinesterase activity. Clinically adequate spontaneous recovery (TOF% > or = 70%) of the mivacurium block with placebo required 15-18 min. On average, clinically adequate antagonism of mivacurium by edrophonium was 50% faster than placebo and 30%-40% faster than with neostigmine. In summary, the speed of antagonism with edrophonium is faster than with neostigmine when antagonizing deep mivacurium NM block.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of mivacurium neuromuscular block: neostigmine versus edrophonium. 748 38


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