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)

Laboratory and clinical evidence of the inhibition of plasma cholinesterase by metoclopramide was demonstrated. When succinylcholine is used as the substrate and the product choline assayed by choline oxidase-peroxidase-quinone dye colorimetry, the rate of the choline production as optical density change was reduced to 50% by 19.5 X 10(-6) M metoclopramide at 20 degrees C. Prolongation of neuromuscular blockade produced by concurrent administration of succinylcholine and metoclopramide was studied in 22 patients aged between 18 and 40 years undergoing elective gynecological surgery. EMG activity in the adductor pollicis muscle was recorded in response to a train-of-four (TOF) stimulus delivered every 10 s. Patients were randomly divided into two groups: A and B. In both groups, anesthesia was induced with thiopental and maintained with sufentanil and nitrous oxide. Tracheal intubation followed intravenous succinylcholine. Intraoperatively, after returning of neuromuscular function, patients in both groups received 20 mg succinylcholine for the determination of duration of neuromuscular blockade. Time from 95% suppression of baseline twitch following a 20 mg increment of succinylcholine until recovery to 25% of control activity was determined. Thereafter, in group A, patients receive metoclopramide (10 mg iv) followed by succinylcholine 20 mg iv, and patients in group B received succinylcholine 20 mg iv alone. Recovery times were again measured and found to be prolonged in patients receiving metoclopramide compared with those not receiving metoclopramide (P less than 0.05). Metoclopramide has no intrinsic neuromuscular blocking activity, but its ability to inhibit plasma cholinesterase probably is the mechanism by which it prolongs succinylcholine block. Reducing the dose of succinylcholine may be appropriate when metoclopramide is given concurrently.
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PMID:Prolongation of succinylcholine block by metoclopramide. 265 89

Metoclopramide and ranitidine (10(-6)-10(-4) M) enhanced the electrical field stimulation-evoked contractions of isolated rat fundus and increased the gastric emptying in conscious rats. The enhancement of the fundus contractions by metoclopramide and ranitidine was abolished by atropine, but not by yohimbine, hexamethonium, propranolol or methysergide. The electrical field stimulation-evoked [3H]outflow from rat fundus strips, which has been preincubated with [3H]choline, was reduced by tetrodotoxin (10(-6) M) or in calcium-free medium, and potentiated by 4-amino-pyridine (3 X 10(-4) M), an acetylcholine (ACh)-releasing agent. Metoclopramide and ranitidine (10(-6)-10(-4) M) did not increase the [3H]outflow from the strips, in spite of causing a significant enhancement of their contractile response. However, both agents caused an increase in the ratio of [3H]acetylcholine/[3H]choline released into the superfusate during electrical field-stimulation. In rat fundus homogenates, metoclopramide and ranitidine showed a significant cholinesterase inhibition. These results seem to cast a doubt on the generally held ACh release hypothesis for the action mechanism of metoclopramide on one hand, and suggest, on the other hand, that cholinesterase inhibition contributes to some extent to the gastrokinetic effects of metoclopramide and ranitidine.
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PMID:Effect of metoclopramide and ranitidine on acetylcholine release from isolated rat stomach. 324 40

Metoclopramide (MCP) in a sufficiently high concentration (100 microM) induced a large and persisting potentiation of slow-excitatory postsynaptic potentials (s-epsp) and slow-inhibitory postsynaptic potentials (s-epsp) but depressed in fast epsp. This modulatory action of metoclopramide was markedly suppressed by (+)-butaclamol (7 microM) and, to a lesser extent, by spiroperidol (2.5-4 microM). Metoclopramide also possessed weak anti-acetylcholinesterase activity(I50% = 245 microM; measured by Dr N. Inestrosa), but this was shown not to account for the potentiating actions of metoclopramide. Thus, although metoclopramide is a D-2 antagonist, it appears to mimic the D-1 action of dopamine in modulating the slow psps.
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PMID:Metoclopramide mimics a D-1 type of dopamine action in rabbit superior cervical ganglion. 711 May 32

KW-5092 ((1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]- 2-imidazolidinylidene) propanedinitrile fumarate) is a novel gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory activity and acetylcholine (ACh) release facilitatory activity. The present study examined the effects of KW-5092 on gastrointestinal (GI) propulsion in rats. KW-5092 at 1 to 30 mg/kg, p.o. dose-dependently enhanced the gastric emptying, small intestinal propulsion and the proximal and distal colonic propulsion. Metoclopramide, a dopamine D2-receptor antagonist with ACh release facilitatory activity, dose-dependently enhanced the gastric emptying at 0.03 to 1 mg/kg, p.o., whereas this drug did not affect the small intestinal propulsion, or the proximal and distal colonic propulsion. Neostigmine, an AChE inhibitor, dose-dependently enhanced the small intestinal propulsion and the proximal and the distal colonic propulsion at 0.3 to 10 mg/kg, p.o., whereas it delayed the gastric emptying at 10 mg/kg, p.o. The present results demonstrate that KW-5092 enhances the GI propulsion from the stomach to the colon and that metoclopramide or neostigmine enhances only the upper or the lower GI propulsion, respectively. Thus, KW-5092 may be a gastroprokinetic drug of a novel type for the treatment of GI motility dysfunctions in a wide range from the stomach to the colon.
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PMID:Stimulating effects of KW-5092, a novel gastroprokinetic agent, on the gastric emptying, small intestinal propulsion and colonic propulsion in rats. 774 44

Mivacurium is metabolized by plasma cholinesterase (PCHE). Metoclopramide inhibits PCHE in vitro and in vivo. We have assessed the effect of metoclopramide on duration of action of mivacurium and measured PCHE at baseline and at the time of maximal block. In a randomized, double-blind study, 30 patients received metoclopramide 0.15 mg kg-1 i.v. or saline, followed by propofol anaesthesia and mivacurium 0.15 mg kg-1. Using a TOF-Guard accelerometer, times to recovery of TI to 25%, 75% and 90% were 13.4, 19.3 and 21.9 min in the saline group and 17.8, 25.3 and 28.8 min in the metoclopramide group (P < 0.01, P < 0.05, P < 0.05, respectively). There were no differences in onset time or recovery index between the groups. PCHE activity at the time of maximum block decreased within each group (P < 0.01) but there was no difference between groups. In a second biochemical study of eight patients, a small decrease in PCHE activity was detected after metoclopramide 0.15 mg kg-1, but before administration of mivacurium (P < 0.025). We conclude that metoclopramide prolongs the duration of action of mivacurium.
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PMID:Influence of metoclopramide on plasma cholinesterase and duration of action of mivacurium. 1047 19

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonine receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP is a reversible inhibitor of cholinesterases from human central nervous system and blood. MCP may have a cholinesterase protective effect against inhibition by organophosphates. The purpose of the study was to quantify "in vitro" by means of the IC(50)-shift the extent of MCP conferred protection, using paraoxon (POX) as an inhibitor. POX is a widely used organophospate responsible for a large number of accidental or suicidal exposures. Cholinesteratic activities (ChE) (with acetyl-thiocholine (A) and butyryl-thiocholine (B) as substrates) in human plasma were measured photometrically in the presence of different POX concentrations and IC(50) was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the shift induced by the presence of MCP increases with the MCP concentration in a linear manner. In the presence of a clinically easily achievable plasma concentration of 1 micro M MCP the IC(50) of POX for ChE 'shifts' by a factor of approximately 2-3. The protective effect of metoclopramide on cholinesterases could be of practical relevance in the treatment of paraoxon poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.
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PMID:In vitro protection of plasma cholinesterases by metoclopramide from inhibition by paraoxon. 1251 40

This study evaluated the protective effect of the benzamide compound metoclopramide (MCP) against inhibition by paraoxon (POX) as assessed by red blood cell acetylcholinesterase (RBC-AChE) activity. Three groups of 6 rats each were used. All substances were applied ip daily for 5 d, followed by a 2-d rest. The 7-d cycle was repeated 6 times. Group 1 received 100 nM POX, Group 2 received 50 microM MCP. Group 3 received 100 nM POX + 50 microM MCP. Red blood cell acetylcholinesterase measurements were performed at base line and then after each 7-d cycle. Enzyme activities were compared using the Mann-Whitney rank order test. Metoclopramide conferred significant in vivo protection from inhibition of RBC-AChE by POX.
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PMID:Metoclopramide protection of cholinesterase from paraoxon inhibition. 1451 94

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition, MCP is a reversible inhibitor of cholinesterases from the human central nervous system and blood, and may have a red blood cell (RBC) acetylcholinesterase (AChE) protective effect against inhibition by organophosphates. The purpose of the study was to quantify 'in vitro', by means of the IC50 shift, the extent of MCP conferred protection, by using paraoxon (POX) and mipafox (MPFX) as inhibitors. Paraoxon is a widely used non-neuropathic organophospate responsible for a large number of accidental or suicidal exposures. Mipafox is a neuropathic organophospate. Red blood cell AChE activities in human plasma were measured photometrically in the presence of different POX, MPFX and MCP concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the IC50 shift induced by the presence of MCP increases with the MCP concentration in a linear manner. The protective effect of MCP on cholinesterases could be of practical relevance in the treatment of POX and MPFX poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.
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PMID:In vitro protection of red blood cell acetylcholinesterase by metoclopramide from inhibition by organophosphates (paraoxon and mipafox). 1463 69

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP is a reversible inhibitor of cholinesterases from human central nervous system and blood. Metoclopramide may have a cholinesterase protective effect against inhibition by organophosphates. The purpose of the study was to quantify in vitro, by means of the IC(50) shift, the extent of MCP conferred protection, using mipafox (MPFX) as an inhibitor. Mipafox is a neuropathic organophosphate. Cholinesterase activities (with acetylthiocholine [ChE-A] and butyrylthiocholine [ChE-B] as substrates) in human plasma were measured photometrically in the presence of different MPFX concentrations and the IC(50) was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the shift induced by the presence of MCP increases with the MCP concentration in a linear manner. In the presence of a clinically easily achievable plasma concentration of 1 micro M MCP, the IC(50) of MPFX for cholinesterase 'shifts' by a factor of ca. 3-6. The protective effect of MCP on cholinesterase could be of practical relevance in the treatment of organophosphate poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.
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PMID:In vitro protection of plasma cholinesterases by metoclopramide from inhibition by mipafox. 1505 10

The benzamide compound metoclopramide (MCP) protects against cholinesterase inhibition by paraoxon (POX) both in vitro and in vivo. This study evaluates MCP-conferred protection of enzyme activity head to head against the therapeutic gold standard pralidoxime (PRX). Six groups of rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day rest. The 7-day cycle was repeated eight times. Group 1 received 100 nM POX, group 2 received 50 micro M MCP, group 3 received 100 nM POX + 50 micro M MCP, group 4 received 50 micro M PRX, group 5 received 100 nM POX + 50 micro M PRX and group 6 received saline. Red blood cell acetylcholinesterase (RBC-AChE) measurements were performed at baseline and on day 5 of each 7-day cycle. The sums of enzyme activities over time (weekly values expressed as % of baseline of 100%) were compared using the Mann-Whitney rank order test. A Bonferroni correction of 4 for multiple comparisons was applied. Paraoxon significantly reduced enzyme activities when compared with saline (Sigma = 535 +/- 25 vs 902 +/- 42). Metoclopramide conferred statistically significant in vivo protection from inhibition of RBC-AChE by POX (Sigma = 640 +/- 58). The extent of protection was significantly less than that conferred by the gold standard PRX (Sigma = 765 +/- 57). Metoclopramide, in addition to being less effective as an RBC-AChE protective agent, also caused a failure to thrive in the POX+MCP-exposed rats, as evidenced by the changes in body weight.
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PMID:In vivo metoclopramide protection of cholinesterase from paraoxon inhibition: direct comparison with pralidoxime in subchronic low-dose exposure. 1530 Jul 12


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