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)

Activities of enzymes cholinesterase (ChE) and carboxylesterase (CaE) were assayed in serum, liver microsomes and three regions of brain, viz; cerebrum, cerebellum and brain stem (with mid brain) in male albino rats at 0.5 and 2 h periods after administration of 1/2 LD 50 dose of soman (0.22 mg/kg) intraperitoneally in olive oil as vehicle. At 0.5 h, in serum, ChE activity declined to 33% of its initial level whereas CaE activity was almost completely inhibited. However, in the liver microsomes at this period, ChE activity was greatly inhibited (18% of initial level) whereas CaE activity was nearly unaffected. At 2 h period, both the enzymes in the serum were almost completely inhibited. In the brain regions (excepting in cerebellum), both the enzymes were nearly similarly inhibited (by 55% to 65% of the initial level) at both the periods. The time related differential response of these two beta-esterases in acute soman intoxication probably occurred in the peripheral tissues like blood and liver but not in the CNS.
 ...
PMID:Effect of soman administration on beta-esterases in blood, liver microsomes and brain regions of rats. 147 52

Heptastigmine is a new long acting cholinesterase inhibitor that affects behaviour in a number of cognitive tests in animals. We have studied its pharmacokinetics in rats: plasma kinetics were evaluated after single intravenous dose (2 mg/kg), intramuscular (4 mg/kg) and oral (4 and 8 mg/kg) administration. Tissue distribution (heart, liver, kidney and brain) was studied after single intramuscular (4 mg/kg) and oral (8 mg/kg) administration. Plasma and tissue kinetics were also investigated after repeated oral doses (8 mg/kg b.i.d. for 7 days). Heptastigmine levels in plasma and tissues were determined using an HPLC method with an electrochemical detector. After a single dose, heptastigmine remained for a long time in plasma (the terminal half-life was about 12 h), distributed widely in tissues (the volume of distribution was about 61) and brain concentrations were very high (4-22 times those found in plasma). After repeated oral doses, the drug levels increased in plasma and, to a lesser extent, in liver and kidney.
 ...
PMID:Pharmacokinetics of heptastigmine in rats. 163 92

The distribution, metabolism, and pharmacokinetics of physostigmine (Phy) and the time course of butyrylcholinesterase (BuChE) in plasma and cholinesterase (ChE) activity in brain and muscle and their relationship to Phy concentration were described after oral administration of 3H-Phy (650 micrograms kg-1) to rats. Physostigmine concentration vs time data was analyzed by nonlinear computer fitting program using one-compartment model. The absorption rate constant (ka) and elimination rate constant (ke) were found to be 0.1 +/- 0.07 min-1 and 0.036 +/- 0.024 min-1, respectively. Cpmax and tmax were 3.3 ng ml-1 and 16 min. The clearance (C1) was found to be 80.9 ml min-1kg-1. Half-life of Phy in brain, muscle, and liver were 33.4 min, 22.5, and 28 min, respectively. The bioavailability (F) was calculated to be 0.02 and the extraction ratio was found to be 0.98 indicating the 'first pass' effect. Butyrylcholinesterase activity in plasma was 76 per cent at 15 min and this activity did not change significantly up to 120 min. However, Phy concentration in plasma was very low; 2.89 ng ml-1 at 15 min and declined to 0.71 ng ml-1 at 90 min. Physostigmine concentration in brain peaked at 22 min to 2.85 +/- 1.09 ng g-1 and declined to 0.33 +/- 0.11 ng g-1 at 60 min. Cholinesterase activity in brain was 96 per cent, 82 per cent and 89 per cent at 10, 45, and 120 min, respectively. Physostigmine concentration in muscle was very low and the ChE activity in the muscle was 66.4 per cent of control at 45 min. The time course of Phy metabolism indicated that at 5 min most of the RA in the tissues was due to metabolites accounting for 94.6 per cent in plasma, 90 per cent in liver, 79.8 per cent in brain and 86.3 per cent in muscle. M1 appeared to be the major metabolite followed by eseroline. The results showed extremely low concentrations of Phy (200 times less in plasma and 350 times less in brain) after oral administration compared to our previous studies with the same dose after i.m. administration.
 ...
PMID:Pharmacokinetics and pharmacodynamics of physostigmine in the rat after oral administration. 270 18

The effects on behavior and cholinesterase (ChE) of an OP pesticide, dimethoate, were examined in wood mice under laboratory conditions. Mice were administered 0, 5, 15, or 50 mg/kg intraperitoneal dimethoate and their behavior was recorded in an open field for one hour. In a second experiment, using only the 0 and the 50 mg/kg dose, mice were subjected to 10-min open field tests repeated at various time intervals during a 24-h period. Shortly after administration of dimethoate, there was a general, dose-dependent, behavioral depression that was characterized by increased inactivity and decreased grooming, rearing, and sniffing. The introduction of a novel object in the open field failed to elicit any reaction in mice treated with the two highest doses of dimethoate. The behavioral impairment completely disappeared 6 h after treatment. A stereotyped compulsive grooming was also observed in the first 30 min after administration of the two highest doses. Exposure to dimethoate caused a dose-dependent decrease in ChE activity in the brain and in serum. Behavioral impairment was associated with maximum levels of ChE inhibition of 65-75% (brain) and 75-85% (serum). Recovery of ChE activity lagged behind that of behavioral impairment and started 3-6 h after dimethoate administration. The possible implications for free-living wood mice which inhabit cereal fields and may be exposed to OPs are discussed.
 ...
PMID:Behavioral and physiological effects of acute sublethal exposure to dimethoate on wood mice, Apodemus sylvaticus. 868 95

Cholinesterase activities in rat forebrain, erythrocytes, and plasma were assessed after a single oral administration of metrifonate or dichlorvos. In 3-month-old rats, the dichlorvos (10 mg/kg p.o.)induced inhibition of cholinesterase reached its peak in brain after l5-45 min and after 10-30 min in erythrocytes and plasma. Cholinesterase activity recovered rapidly after the peak of inhibition, but did not reach control values in brain and erythrocytes within 24 h after drug administration. The recovery of plasma cholinesterase activity, in contrast, was already complete 12 h after dichlorvos treatment. Metrifonate (100 mg/kg p.o.) had qualitatively similar inhibition kinetics as dichlorvos, albeit with a slightly delayed onset. Peak values were attained 45-60 min (brain) and 20-45 min (blood), after drug administration. Apparently complete recovery of cholinesterase activity was noted in both tissues 24 h after treatment. The dose-dependence of drug-induced inhibition of cholinesterase in rat blood and brain was determined at the time of maximal inhibition, i.e., 30 min after dichlorvos treatment and 45 min after metrifonate treatment. The oral ED(50) values obtained for dichlorvos were 8 mg/kg for brain and 6 mg/kg for both erythrocyte and plasma cholinesterase. The corresponding oral ED(50) values for metrifonate were 10 to 15 times higher, i.e., 90 mg/kg in brain and 80 mg/kg in erythrocytes and plasma. In rats deprived of food for 18 h before drug treatment, the corresponding ED(50) values for metrifonate were 60 and 45 mg/kg, respectively, indicating an about two-fold higher sensitivity of fasted rats to metrifonate-induced cholinesterase inhibition compared to non-fasted rats. Compared to 3-month-old rats, 19-month-old rats showed a higher sensitivity towards metrifonate and dichlorvos. At the time of maximal inhibition, there was a strong correlation between the degree of cholinesterase inhibition in brain and blood. These results demonstrate that single oral administration of metrifonate and dichlorvos induces an inhibition of blood and brain cholinesterase in the conscious rat in a dose-dependent and apparently fully reversible manner. While the efficiency of a given dose of inhibitor may vary with the satiety status or age of the animal, the extent of brain ChE inhibition can be estimated from the level of blood ChE activity.
 ...
PMID:Metrifonate and dichlorvos: effects of a single oral administration on cholinesterase activity in rat brain and blood. 913 40

Five organophosphates: tribufos, oxydemeton-methyl, fenamiphos, coumaphos, and trichlorfon were evaluated for their potential to produce reproductive and neonatal toxicity following continuous dietary exposure during multigenerational reproduction toxicity studies in the Sprague-Dawley rat. Dietary concentrations were selected to demonstrate parental effects in the high dose and provide for a no-adverse effect level at the low dose. There were no clinical signs observed in the adults or neonates during either generation. Significant effects on body weight and food consumption, when observed, were typically observed only with the highest dietary concentration and were greater in the second generation. Reproductive effects, including decreased fertility and mating indices, were only observed with test compounds and at dietary concentrations demonstrating effects on body weight and/or food consumption. Similarly, pup body weight was also affected by those test compounds that produced significant maternal effects during lactation. Significant inhibition of parental cholinesterase activities (plasma, erythrocyte, and brain) was similarly observed in both generations with all test compounds, with at least the highest concentrations. In general, females demonstrated greater enzyme inhibition than the males. For example, mean PChe inhibition considering both generations and all test compounds was 74% for the females, whereas inhibition was 51% in the males. Effects on cholinesterase activities in the neonates (Lactation Day 4) were, for most test compounds, below 10% at the highest dietary concentration. However, by Lactation Day 21, inhibition of enzyme activity (considering all test compounds at the highest concentration and all enzymes) was approximately 30%. The increase in inhibition is attributed to the consumption of the treated feed during the latter stages of lactation. Considering the relative maternal (termination) and neonatal (Lactation Day 4) cholinesterase effects at the highest dietary concentration, it was observed that the effects in the neonate were, for all organophosphates tested, significantly less than those observed in the dam.
 ...
PMID:Comparative organophosphate-induced effects observed in adult and neonatal Sprague-Dawley rats during the conduct of multigeneration toxicity studies. 987 97

Spontaneous motor activity, rota-rod performance (motor co-ordination), body weight gain, food intake, activities of total cholinesterase (blood) and acetylcholinesterase (brain), and dental structure were determined in adult female rats treated with a very high dose of sodium fluoride (500 ppm in drinking water) alone and in combination with calcium carbonate (50 mg/kg body weight by oral intubation) for 60 days. The concentration of fluoride and calcium were measured in the serum of these animals. Administration of sodium fluoride with drinking water produced both behavioural and dental toxicities and not lethality in the present study. A suppression of spontaneous motor activity, a shortening of rota-rod endurance time, a decreased body weight gain and food intake, a suppression of total cholinesterase and acetylcholinesterase activities and dental lesion were observed in test animals. Serum fluoride concentration was raised markedly and that of calcium was decreased in these animals. The effects of sodium fluoride were prevented significantly when animals received calcium carbonate along with sodium fluoride. Serum fluoride content was decreased and that of calcium was restored to control level in these animals. These results indicate that calcium prevents not only fluoride-induced hypocalcemia but also the locomotor behavioral and dental toxicities of fluoride by decreasing bioavailability of fluoride.
 ...
PMID:Calcium preventing locomotor behavioral and dental toxicities of fluoride by decreasing serum fluoride level in rats. 1129 76

CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor of AChE, it is 115 times more potent against this enzyme than against butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition of central (brain) AChE than peripheral (heart) AChE. In vivo CHF2819, 0.5, 1.5, and 4.5 mg/kg p.o., significantly and in dose-dependent manner increased acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging animals, with lower basal ACh levels than young adult rats, also exhibit a marked increase in hippocampal levels of this neurotransmitter after administration of CHF2819. At 1.5 mg/kg p.o. CHF2819 attenuated scopolamine-induced amnesia in a passive avoidance task. Furthermore, it decreased dopamine (DA) levels and increased extracellular levels of 5-hydroxytryptamine (5-HT) in the hippocampus, without modifying norepinephrine (NE) levels. By oral administration to young adult rats CHF2819 did not affect extracellular hippocampal levels of glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine (Tau), arginine (Arg) or citrulline (Cit). Functional observational battery (FOB) screening demonstrated that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological endpoints (body weight and temperature). CHF2819 induced, however, involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a dose-dependent manner. The neurochemical and behavioral profiles of CHF2819 suggest that this orally active novel AChEI could be of clinical interest for the treatment of Alzheimer-type dementia associated with multiple neurotransmitter abnormalities in the brain. In particular, CHF2819 might be a useful therapeutic drug for AD patients with cognitive impairment accompanied by depression.
 ...
PMID:CHF2819: pharmacological profile of a novel acetylcholinesterase inhibitor. 1207 May 26

The accepted mechanism of toxicity of many organophosphorous and carbamate insecticides is inhibition of acetylcholinesterase activity. In mammals, part of the toxicity assessment usually includes monitoring blood and/or brain acetylcholinesterase inhibition. Other tissues, however, contain cholinesterase activity (i.e. acetyl- and butyryl-cholinesterase), and the inhibition of that activity may be informative for a full appraisal of the toxicity profile. The present group of studies first optimized the variables for extraction and solubilization of cholinesterase activity from various rat tissues and then refined an existing automated method, in order to differentially assess acetyl and butyrylcholinesterase activity in those tissues. All these studies were conducted using tissues from untreated, Long-Evans, adult rats. The first studies determined the effect of Triton X-100 or salt (NaCl) on the extraction and solubilization of cholinesterase activity from retina, brain, striated muscle, diaphragm, and heart: phosphate buffer plus detergent (1% Triton X-100) yielded the highest activity for most tissues. For striated muscle, however, slightly more activity was extracted if the phosphate buffer contained both 1% Triton X-100 and 0.5 M NaCl. It was also noted that the degree of homogenization of some tissues (e.g. striated muscle) must be increased for maximal solubilization of all cholinesterase activity. Subsequent studies developed a method for assessing the level of acetylcholinesterase, butyrylcholinesterase and total cholinesterase activity in these tissues using an automated analyzer. In conclusion, automated assay of acetylcholinesterase activity in cholinergically innervated tissues in the rat (other than brain) is achievable and relatively convenient.
 ...
PMID:Automated measurement of acetylcholinesterase activity in rat peripheral tissues. 1262 16

Trahira (Hoplias malabaricus) used to investigate the effects of successive Pb(II) or tributyltin (TBT) dietary doses. After 70 days of acclimation, individuals were exposed to 21 microg Pbg(-1) or 0.3 microg TBTg(-1) (5-day intervals, 14 doses). Two experiments were conducted to investigate the histopathological effects (liver and kidney) and measure the cholinesterase activity (muscle and brain) after Pb(II) or TBT dietary doses. A number of morphological effects were observed in liver, including cytoskeleton disturbance, microautophagy of mitochondria, nuclear damage, and cell death. In kidney, necrosis area, increasing of the neutrophils cell number, changes in melano-macrophage centers, and free macrophages were frequently registered after both Pb(II) and TBT exposures. The cholinesterase activity was inhibited in muscle after 14 doses of Pb(II), but no effects were found in individuals exposed to TBT. In summary, this work is the first to report detailed in vivo toxic effects in tropical fish, H. malabaricus, after dietary sublethal exposure to Pb(II) and TBT.
 ...
PMID:Effects of dietary Pb(II) and tributyltin on neotropical fish, Hoplias malabaricus: histopathological and biochemical findings. 1554 30


1 2 Next >>