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)

We have recently reported that acute intraperitoneal administration of pyridostigmine bromide to rats resulted in significant decrements in physical performance in the heat, adverse thermoregulatory effects, and exacerbated elevations in several indices of heat/exercise injury. Since it will be consumed orally as a prophylaxis for organophosphate poisoning, pyridostigmine was dissolved in the drinking water of rats. Consumption of pyridostigmine for 7 days (n = 34, 6.6 mg/day) resulted in a 23% (p less than 0.001) reduction of circulating cholinesterase when compared with a control group (n = 31) while ingestion for 14 days (n = 35, 8.9 mg/day) elicited a 39% (p less than 0.001) inhibition of circulating cholinesterase when compared to a second control group (n = 33). Water and food consumption, rate of weight gain, and overt behavior were unaffected by pyridostigmine consumption. When approximately half the animals in each group were exercised (9.14 m/min) in the heat (35 degrees C) to hyperthermic exhaustion (Tre = 42.5-43 degrees C, rats unable to right themselves), pyridostigmine consumption for 14 days effected a significantly (p less than 0.05) increased rate of weight loss, but no further effects on thermoregulation or performance were noted. Several minor increments were observed in clinical indices of heat/exercise injury in rats consuming pyridostigmine for 14 days. These data indicate that oral dosages of pyridostigmine can probably be titrated to levels of cholinesterase inhibition which are efficacious in prophylaxis against organophosphate toxicity without significant effects on selected physiologic and metabolic processes.
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PMID:Oral pyridostigmine administration in rats: effects on thermoregulation, clinical chemistry, and performance in the heat. 378 59

The neuromuscular junctions from diaphragm, soleus, and extensor digitorum longus (EDL) muscles of male albino rats were assessed for morphological alterations following acute (30-min) and subacute (2-day) exposure to pyridostigmine bromide in Mestinon-equivalent buffer. These muscles were selected to compare the effects of the drug on muscles of different fiber type composition. The diaphragm has approximately equal numbers of type I and type II fibers while the soleus and EDL possess primarily type I and type II fibers, respectively. Pyridostigmine was administered to each acute-exposure animal by a single subcutaneous injection of 0.36 mg/kg pyridostigmine and to each subacute-exposure animal by a subcutaneously implanted osmotic minipump containing 10 mg/ml pyridostigmine. Both treatments resulted in whole blood cholinesterase (ChE) depression of approximately 60-70% as determined by radiometric assay. Control animals received only Mestinon-equivalent buffer. Both acute and subacute exposures resulted in morphological alteration of the neuromuscular junctions (NMJs) of all three muscles, although considerable variation in the extent of damage occurred even within individual NMJs. The most frequently observed presynaptic alterations were mitochondrial damage and partial withdrawal of nerve terminal branches (partial denervation). Post-synaptic changes included occasional rarefaction of mitochondrial matrices and disruption of the myofibrillar organization in small numbers of subjunctional sarcomeres. The data indicate that acute or subacute exposure to pyridostigmine bromide at a whole blood ChE depression of 60-70% results in similar alterations to the NMJs of three muscles with substantially different fiber type compositions. Although the severity of the damage varies from fiber to fiber, the variability appears random and not related to a specific fiber type or dosage regimen.
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PMID:Neuromuscular toxicity of pyridostigmine bromide in the diaphragm, extensor digitorum longus, and soleus muscles of the rat. 409 93

1. Reactivation of erythrocyte cholinesterase inhibited by ethyl p-nitrophenyl ethylphosphonate (armine) was studied with NN'-dimethylenebis-(4-hydroxy-iminomethylpyridinium bromide) (C(2)-oxime), NN'-trimethylenebis-(4-hydroxy-iminomethylpyridinium bromide) (C(3)-oxime), NN'-tetramethylene-(4-hydroxy-iminomethylpyridinium bromide) (C(4)-oxime) and NN'-pentamethylenebis-(4-hydroxyiminomethylpyridinium bromide) (C(5)-oxime) as reactivators. The kinetics of reactivation were consistent with a reaction of the type: [Formula: see text] and bimolecular rate constants for reactivation were calculated from the corresponding differential equations. 2. Of the four oximes studied C(2)-oxime was least effective and the other three oximes were about equally effective reactivators. 3. Reactivation of armine-inhibited cholinesterase by C(3)-oxime was also studied in the presence of substrate. This reaction was first-order with respect to inhibited enzyme, and slower than in the absence of substrate.
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PMID:Oxime reactivation of erythrocyte cholinesterase inhibited by ethyl p-nitrophenyl ethylphosphonate. 588 60

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

HGG12 and HGG42 are effective therapeutic agents in experimental organophosphate poisoning even after "aging" of the phosphonylated cholinesterase (Hauser, Kirsch, Weger, 1981). In this study we investigated their action in the isolated superior cervical ganglion of the rat (SCGR) after cholinesterase inhibition by Soman (.4 microM). As these two compounds have ganglion blocking properties (Kirsch, Weger, 1981), the action of hexamethonium bromide (C6) and atropine was also investigated and compared to theirs. The typical effects of Soman in the SCGR are a block of ganglionic transmission within 10 sec in a test train of stimuli of 6 Hz, 30 sec, and an increase of the NAD(P)H-fluorescence response up to 3 times the control value. Addition of HGG12 or HGG42 in a concentration of 30-60 microM restores transmission and decreases the metabolic response to almost normal values while obidoxime (60 microM) has no effect at all. C6 (117 microM) and to a lesser degree atropine (30-60 microM) also improve ganglionic transmission and the metabolic response in cholinesterase poisoning. The pattern of amplitudes of APs in a test train of stimuli however is only restored by the HGG compounds and a comparison of equipotent concentrations (50% inhibition of AP in unpoisoned ganglia) shows that HGG12 has the best effects in Soman poisoned SCGR. The superiority of HGG12 can be explained by an inhibitory action of HGG12 on both nicotinic and muscarinic ganglionic receptors.
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PMID:Effect of the bispyridinium oximes HGG12 and HGG42 and ganglion blocking agents on synaptic transmission and NAD(P)H-fluorescence in the superior cervical ganglion of the rat after Soman poisoning in vitro. 613 39

Antagonism of neuromuscular block using cholinesterase inhibitors and atropine is charged with several risks, which are at least partly caused by pharmacological characteristics of the anticholinergic drugs, e.g. short duration of action causing secondary bradycardia. Compared to atropine, ipratropium bromide, a new anticholinergic drug, is--due to its quarternary ammonium compound--characterized by longer duration of action. In contrast to atropine, this substance does not penetrate the blood-brain and placental barrier. Our present study was designed to compare the haemodynamic effects of both substances, using invasive monitoring, during antagonism of neuromuscular block with pyridostigmine. In contrast to atropine, ipratropium bromide induced a higher degree of initial tachycardia but did not allow secondary reduction of heart rate by rebound vagal stimulation. While cardiac output was almost constant, ipratropium bromide caused changes in stroke volume, which were due to alterations in heart rate. There were no clinically relevant changes of the other haemodynamic parameters. Cardiac arrhythmia were observed more often after administration of atropine and were of longer duration. In conclusion, ipratropium bromide is a useful alternative to atropine in patients with pre existing low heart rate and bradyarrhythmia.
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PMID:[Hemodynamic effects in antagonism of neuromuscular blockage: atropine-pyridostigmine versus ipratropium bromide-pyridostigmine]. 623 62

The acetylcholinesterase (AchE) inhibitory effect of a muscle relaxant 2 beta,16 beta-bis-(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), was studied in vitro. The inhibition of AchE activity of human red blood cells, expressed as pI50, was 3.99, whereas that of serum cholinesterase (ChE) was 4.33. The AchE inhibitor action was reversible. The inhibition was not influenced by the combined administration of promethazine or atropine. The combined effect of pipecurium bromide and of some other diamino-azasteroid agent proved to be additive. Pipecurium bromide showed mixed-type inhibitory effect both on AchE and ChE.
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PMID:The effect of the steroid muscle relaxant pipecurium bromide on the acetylcholinesterase activity of red blood cells in vitro. 624 79

In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) or the cholinergic muscarinic receptor agonist oxotremorine (0.25 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Complete suppression of the GH-releasing effect of eserine and oxotremorine was induced by blockade of cholinergic muscarinic receptors by atropine (80 or 20 micrograms/kg, 30 min before) but not by scopolamine-N-butyl bromide (0.8 mg/dog, 30 min before), an anticholinergic drug which does not cross the blood brain barrier (BBB). In contrast, activation of cholinergic nicotinic receptors by nicotine (6 mg) failed to alter resting cGH concentrations, and pre-treatment with the nicotinic receptor blocker mecamylamine (5 mg, 30 min before) did not counteract the GH-releasing effect of eserine. Other cholinomimetic drugs, e.g. pilocarpine, 4-aminopyridine, carbachol and bethanechol failed to induce a rise in plasma cGH concentrations. These data indicate that: 1) cholinergic muscarinic but not nicotinic receptors located in the central nervous system (CNS) inside the BBB play a facilitatory role in tonic cGH release; 2) pharmacologically distinct muscarinic receptors may exist in the CNS.
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PMID:Effect of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog. 630 74

A modified method of Ellman's reaction with a continuous flow was used to study the cerebral cholinesterase activity in its biological environment with rat brain slices including the striatum. Comparative studies were performed under various conditions of flow and substrate concentrations (acetylthiocholine bromide) and with or without formaldehyde fixation. We could thus measure either the inhibition rate of cerebral ChE by paraoxon or MPT or the reactivation rate by some oximes in the presence of substrate and after removing excess inhibitor.
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PMID:In vitro study of organophosphorus inactivators of membrane acetylcholinesterase and of reactivating pyridinium-oximes using rat brain slices. 641 4

The effects of spinal cord transection and acidosis on succinylcholine (SCC)-induced hyperkalemia were studied in Sprague-Dawley rats. The effectiveness of pretreatment with subparalyzing doses ("self-taming") of SCC or with the cholinesterase inhibitor hexafluorenium bromide in preventing hyperkalemia was also studied. The increase in plasma potassium after administration of SCC (1 mg/kg) was found to be significantly increased 10 days after spinal cord transection. This potassium increase could not be prevented by pretreatment with either hexafluorenium (0.3 mg/kg) or subparalyzing doses (0.15 mg/kg) of SCC. Respiratory acidosis caused an increase in plasma K+ in both normal and in spinal cord transected rats. Acidosis had a synergistic effect on succinylcholine-induced hyperkalemia. These findings support the clinical practice of not using succinylcholine in patients at risk of having a pathological sensitivity to SCC. Furthermore, SCC may be especially dangerous when administered to patients who are acidotic.
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PMID:Synergistic effect of acidosis and succinylcholine-induced hyperkalemia in spinal cord transected rats. 671 Dec 67


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