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

Oral toxicity, distribution and metabolism of a new multi-insect repellant, N,N-diethylphenylacetamide (DEPA) was studied in rats. On administration of DEPA (851 mg/kg body wt.) labelled with 14C blood, liver, stomach and stomach contents had 2.65, 3.97, 12.07 and greater than 50.66% radioactivity, respectively, after 20 min. Gas chromatographic analysis showed presence of both DEPA and its metabolite N-ethylphenylacetamide (EPA) in blood, liver, kidneys and lungs while only DEPA was present in stomach and stomach contents. EPA, phenylacetamide and conjugated phenylacetic acid were excreted along with unmetabolized parent compound in urine of rats when a low oral dose of DEPA (70 mg/kg body wt.) was administered. Activities of erythrocyte cholinesterase and carbonic anhydrase did not change significantly upon acute oral exposure to DEPA.
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PMID:Distribution and metabolism of insect repellant N,N-diethylphenylacetamide on oral exposure in rats. 200 66

Cutaneous LD50 of N,N-diethylphenylacetamide (DEPA), a new multi insect repellent was 2200, 3200 and 7100 mg/kg body weight in female mice, rats and guinea pigs; and 1600 and 4000 mg/kg in male mice and rats indicating a high degree of safety on skin contact. Dermal application of DEPA to young growing rats for 21 days at a dose of 50 mg/kg did not exert any adverse effects while massive doses of 500 and 1000 mg/kg caused marked reduction of body weight gain and lowering of activities of serum alanine aminotransferase, aspartate aminotransferase and cholinesterase. Along with DEPA, N-ethylphenylacetamide, phenylacetamide and phenylacetic acid were detected in the urine of DEPA treated mice, rats and guinea pigs.
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PMID:Toxicity and metabolism of a new insect repellent N,N-diethylphenylacetamide in mice, rats and guinea pigs on cutaneous application. 281 93

Plasma aspirin esterase activity and cholinesterase activity were reduced in patients with aspirin sensitive asthma and aspirin sensitive urticaria compared to asthmatic and dermatological controls. Phenylacetate (non specific) esterase activities, were however unaltered in these patients. The reason for the lower activity is uncertain but it does not appear to be due to genetically determined lower cholinesterase or due to the avoidance of aspirin by sensitive patients. A low aspirin esterase activity may be a contributory factor in precipitating these aspirin sensitive reactions.
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PMID:Plasma esterase activity in patients with aspirin-sensitive asthma or urticaria. 344 44

Administration of the irreversible cholinesterase inhibitor isoflurophate (diisopropylfluorophosphate, DFP) before 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) enhanced the loss in tyrosine hydroxylase activity and dopamine and 3,4-dihydroxy-phenylacetic acid content in the striatum of mice in a dose-dependent manner. The effect of DFP on the MPTP-induced changes of dopaminergic markers was evident 30 days after initiating treatment, suggesting augmented neurotoxicity. Neurotoxicity was also enhanced by prior treatment with nicotine, carbachol or oxotremorine. We conclude that activation of either muscarinic or nicotinic receptors enhances the neurotoxicity of MPTP.
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PMID:Enhanced MPTP neurotoxicity after treatment with isoflurophate or cholinergic agonists. 791 17

Esterases in human liver microsomes hydrolysed fluazifop-butyl (Vmax 9.8 +/- 1.6 mumol/min/g tissue), paraoxon (Vmax 47.4 +/- 7.5 nmol/min/g tissue) and phenylacetate (Vmax 57 +/- 8 mumol/min/g tissue), whereas esterases found in the human liver cytosol hydrolysed fluazifop-butyl (Vmax 10.0 +/- 0.5 mumol/min/g tissue) and phenylacetate (Vmax 37 +/- 2.9 mumol/min/g tissue) but not paraoxon. Human plasma esterase hydrolysed fluazifop-butyl (Vmax 0.09 +/- 0.006 mumol/min/mL), paraoxon (Vmax 210 +/- 14 nmol/min/mL) and phenylacetate (Vmax 250 +/- 17 mumol/min/mL). Inhibitory studies using paraoxon, bis-nitrophenol phosphate and mercuric chloride indicated fluazifop-butyl hydrolysis involved carboxylesterase in liver microsomes and cytosol, and cholinesterase and carboxylesterase in plasma. Phenylacetate hydrolysis involved arylesterase in plasma, both arylesterase and carboxylesterase in liver microsomes and carboxylesterase in liver cytosol. Plasma hydrolysis is less important and overall esterase activity is lower in humans than in the rat which is therefore a poor model.
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PMID:Human xenobiotic metabolizing esterases in liver and blood. 821 61

Susceptibility to organophosphorus (OP) insecticides and nerve agents is strongly influenced by genetic and developmental factors. A number of organophosphorothioate insecticides are detoxified in part via a two-step pathway involving bioactivation of the parent compound by the cytochrome P450 systems, then hydrolysis of the resulting oxygenated metabolite (oxon) by serum and liver paraoxonases (PON1). Serum PON1 has been shown to be polymorphic in human populations. The Arg192 isoform (PON1R192) of this HDL-associated protein hydrolyzes paraoxon (POX) at a high rate, while the Gln192 isoform (PON1Q192) hydrolyzes paraoxon at a low rate. The effect of the polymorphism is reversed for the hydrolysis of diazoxon (DZO), soman and particularly sarin. Phenylacetate is hydrolyzed at approximately the same rate by both PON1 isoforms and chlorpyrifos oxon (CPO) slightly faster by the PON1R192 isoform. In addition to the effect of the amino acid substitution on rates of toxicant hydrolysis, two other factors influence these rates. The expression of PON1 is developmentally regulated. Newborns have very low levels of PON1. Adult levels in rats and mice are reached at 3 weeks of age and in humans, sometime after 6 months of age. In addition, among individuals of a given genotype, there is at least a 13-fold difference in expression of PON1 that is stable over time. Dose/response experiments with normal mice injected with purified PON1 and with PON1 knockout mice have clearly demonstrated that the observed differences of in vitro rates of hydrolysis are significant in determining differential sensitivities to specific insecticides processed through the P450/PON1 pathway. Injection of purified rabbit PON1 protects mice from cholinesterase inhibition by chlorpyrifos (CPS) and CPO. Knockout mice are much more sensitive to CPO and DZO than are their PON1+/+ littermates or wild-type mice. A number of recent reports have also indicated that the PON1R192 isoform may be a risk factor for cardiovascular disease. Studies with PON1 knockout mice are also consistent with a role of PON1 in preventing vascular disease.
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PMID:Genetic and temporal determinants of pesticide sensitivity: role of paraoxonase (PON1). 1079 89

The synthetic methodology is carried out in multistep which was initiated as phase I by utilizing Fischer esterification methodology of 2-phenylacetic acid (1) to ethyl-2-phenylacetate (2). The ester was reacted with hydrazine hydrate form 2-phenylacetohydrazide (3) which underwent ring closure with carbon disulfide in alcoholic base to achieve 5-benzyl-1,3,4-oxadiazole-2-thiol (4). Phase II, involved the reaction of electrophiles with 2-bromoacetylbromide (5) with arylated/arenylated amines (6a-e) in aqueous alkaline medium under vigorous shaking to generate N-substituted-2-bromoacetamides (7a-e). Finally in phase III, the parent oxadiazole reacted with N-substituted-2-bromoacetamides and in DMF/LiH to yield 2-[(5-benzyl-1,3,4-oxadiazole-2yl)sulfanyl]-N-(arylated/arenylated) acetamides (8a-e). All the derivatives were screened for their anti-enzymatic potential against acetyl/butyrylcholinesterase and lipoxygenase and for the antibacterial activity. They were found to be weak enzyme inhibitors and also possessed weak antibacterial action with the exception of 8e, which demonstrated prominent anti-enzymatic and antibacterial activity, which may be attributed to the presence of 3,4-dimethoxyphenylacetamide moiety. The LD50 data revealed that most of the N-substituted derivatives were found to be less cytotoxic.
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PMID:Synthesis of 2-[(5-benzyl-1,3,4-oxadiazole-2yl)sulfanyl]-N-(arylated/arenylated) acetamides as antibacterial and acetyl cholinesterase inhibitors. 2908 97