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)

Objective evaluation of muscle relaxation during surgery is possible only by indirect stimulation of a skeletal muscle by means of a peripheral nerve stimulator. Most frequently the ulnar nerve is electrically stimulated and the resulting contraction of the hand muscles, i.e., twitching of the fingers is observed. This direct observation of the finger twitches induced by a nerve stimulator provides valuable information a) on the actual magnitude of neuromuscular blockade, b) on the development of a dual block following suxamethonium, c) on the need for more muscle relaxant, d) on the reversal of muscle paralysis by a cholinesterase inhibiting agent, and finally e) on the differential diagnosis of prolonged postoperative apnoea. By employing a nerve stimulator, the neuromuscular blocking agents can be titrated according to the surgical requirements and overdosage can be avoided. The clinical judgement of muscle relaxation by the anaesthesiologist should be accompanied by a more quantitative and objective evaluation, making use of the nerve stimulator.
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PMID:[On the monitoring of neuromuscular blockade during anaesthesia (author's transl)]. 85 89

In concentrations above 20 microM, (+/-)-meptazinol produced a contraction of the guinea-pig isolated ileum and this effect was antagonized by atropine (0.01 to 0.3 microM) in a manner which was not competitive. Cooling the preparation to 15 degrees C blocked the contractile action of meptazinol and of dimethylphenylpiperazinium (DMPP) but did not affect the action of carbachol. Twitch responses of the rat phrenic nerve-diaphragm preparation induced by indirect electrical stimulation in the presence of naloxone (20 nM) were potentiated by meptazinol (1 to 40 microM) which also reversed a partial blockade of the twitch induced by tubocurarine. Neither of these effects was seen in tissues which had been pretreated with the cholinesterase inhibitor BW284C51 (0.2 microM) though tetraethylammonium iodide (40 microM) was still able to enhance the responses to stimulation. In the presence of naloxone (20 nM) electrically induced responses of the rat isolated rectum were abolished by cinchocaine (10 microM), partially blocked by atropine (0.1 to 0.4 microM) and potentiated by meptazinol (1 to 30 microM). The latter action was not seen when meptazinol was administered in the presence of BW284C51. It is concluded that the cholinergic action of meptazinol in these tissues is due to an indirect effect, probably involving inhibition of cholinesterase and that no evidence was seen of any ability to increase the release of acetylcholine itself.
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PMID:An investigation of the mechanism involved in the cholinergic action of meptazinol. 288 82

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

Anatoxin-a(s) [antx-a(s)] is produced by Anabaena flos-aquae clone NRC 525-17 and is different from anatoxin-a, a known depolarizing agent produced by A. flos-aquae NRC 44-1. Purification of antx-a(s) from lyophilized cells involved extraction with 1.0 M acetic acid: ethanol (80:20), column chromatography (Sephadex G-15 and CM-Sephadex C-25) and high performance liquid chromatography. Purified toxin has an LD50 (i.p., mouse) of approximately 50 micrograms/kg. Gross pharmacological tests of antx-a(s) on isolated chick biventer cervicis and frog rectus abdominis muscles showed no direct agonistic effect. Instead, antx-a(s) augments the acetylcholine response and antagonizes the actions of d-tubocurarine. Twitch potentiation and tetanic fade were observed on isolated rat phrenic nerve--diaphragm muscle when stimulated indirectly at different frequencies. In acute toxicity tests with mice and rats the signs of poisoning were indicative of excessive cholinergic stimulation. Mice pretreated with atropine sulfate showed longer survival times and no parasympathomimetic signs of toxicity. The mice still died of respiratory arrest with convulsions, which indicated that toxicity is due to more than just the peripheral muscarinic action of antx-a(s). Assays of serum cholinesterase of rats in acute toxicity tests showed complete inactivation of the enzyme at doses of 350 and 600 micrograms/kg. It was concluded that antx-a(s) may be acting as an anticholinesterase, thereby causing toxicity.
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PMID:The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17. 308 30

1 Isolated, desheathed preparations of the rabbit rectococcygeus muscle were relatively insensitive to spasmogens other than muscarinic drugs. Transmural stimulation with 1-50 pulses (0.2-0.4 ms at 10 Hz) elicited graded twitches which were abolished by tetrodotoxin and were therefore neurogenic; longer pulses sometimes triggered tetrodotoxin-resistant myogenic contractions.2 Twitches elicited by 0.2-0.4 ms pulses were due to post-ganglionic excitation because they were not reduced by hexamethonium, pentolinium or dimethyltubocurarine, or by ganglion-paralyzing concentrations of nicotine.3 The acetyl- and butyryl-cholinesterase activities of the rectococcygeus were determined manometrically and could be selectively inhibited by BW 284C51 (1:5-bis-(4-allyl-dimethylammonium-phenyl)-pentan-3-one dibromide) and iso-OMPA (tetramonoisopropylpyrophosphortetramide), respectively. Single-pulse twitches were greatly potentiated in amplitude and duration only when both cholinesterases were inhibited.4 The preparations could not be made to contract by nicotine (2.1-21 muM) even after cholinesterase inhibition, suggesting an absence of ganglion-cells; with nicotine (105-210 muM) small, atropine-susceptible responses were elicited, which were non-ganglionic because they were not reduced by tetrodotoxin.5 Rectococcygeus preparations that had been treated with physostigmine released acetylcholine into the bath fluid on electrical stimulation.6 The motor transmission was paralyzed by botulinum toxin (Type A) and abolished by atropine; the block of muscarinic receptors by atropine was effective against both endogenous and exogenous acetylcholine.7 Inhibitory adrenoceptors and scanty motor alpha-adrenoceptors were detected in the smooth muscle.8 Strong inhibitions of motor transmission and of rhythmic activity were produced by noradrenaline (but not by tyramine), by isoprenaline, and, after phentolamine, also by adrenaline and phenylephrine. These inhibitions were only slightly reduced by propranolol and rather more by pindolol.9 Experiments on preparations retaining their extrinsic nerve supply suggest an absence of ganglionic relays in the last 1-2 cm of the motor nerve pathway to this muscle.10 Some contrasting properties of the adjacent caudo-anal muscle, including the poor motor responses to transmural stimulation, are described.
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PMID:The rabbit rectococcygeus: a ganglion-free parasympathetically innervated preparation. 415 88

Embryonic Xenopus muscle cells grown in culture develop discrete patches of high acetylcholine receptor (AChR) density. By following identified muscle cells after staining with fluorescent alpha-bungarotoxin, we have found that many of these AChR patches survive in a fixed position for several days. For AChR patches on the lower surface of the cell (the surface apposed to the culture dish), more than 60% of those which were followed beginning on day 2 survived for a further 4 days. The survival rate was greater when patches were followed from day 3 or later and was almost as high for AChR patches on the upper surface. New AChR patches also formed on all of the muscle cells. When muscle cells were cultured together with spinal cord cells, nerve-muscle contacts developed with a characteristic localization of AChRs along the path of contact. AChR patches did not form elsewhere on these contacted cells. Nerve-contacted muscle cells examined 2 to 3 days after adding spinal cord cells to established (2- to 5-day-old) muscle cultures also exhibited a marked reduction of AChR patches away from the site of contact. This reduction was not due to the nerve having contacted pre-existing AChR patches. Rather, the findings indicate that contact by an appropriate nerve inhibits the formation of AChR patches elsewhere on the contracted muscle cells and reduces the survival of pre-existing AChR patches. Nerve contact also inhibited the formation of cholinesterase (ChE) patches remote from the site of contact and appeared to cause some reduction in the survival of pre-existing ChE patches. Spontaneous twitching was not observed in these experiments, thereby indicating that the remote effects of nerve contact were not mediated by muscle action potentials or contraction. Such remote influences of the nerve may play a role in determining the pattern of innervation on individual muscle cells.
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PMID:Influence of nerve on the formation and survival of acetylcholine receptor and cholinesterase patches on embryonic Xenopus muscle cells in culture. 707 70

Nerve-evoked contractions were studied in vitro in phrenic nerve-hemidiaphragm preparations from strain 129X1 acetylcholinesterase knockout (AChE-/-) mice and their wild-type littermates (AChE+/+). The AChE-/- mice fail to express AChE but have normal levels of butyrylcholinesterase (BChE) and can survive into adulthood. Twitch tensions elicited in diaphragms of AChE-/- mice by single supramaximal stimuli had larger amplitudes and slower rise and decay times than did those in wild-type animals. In AChE-/- preparations, repetitive stimulation at frequencies of 20 and 50 Hz and at 200 and 400 Hz produced decremental muscle tensions; however, stimulation at 70 and 100 Hz resulted in little or no loss of tension during trains. Muscles from AChE+/+ mice maintained tension at all frequencies examined but exhibited tetanic fade after exposure to the selective AChE inhibitor 1,5-bis(4-allyldimethyl-ammoniumphenyl)pentane-3-one (BW 284C51). The ability of diaphragm muscles from AChE-/- mice to maintain tension at 70 and 100 Hz suggests a partial compensation for impairment of acetylcholine (ACh) hydrolysis. Three mechanisms--including a reliance on BChE activity for termination of ACh action, downregulation of nicotinic acetylcholine receptors (nAChRs), and morphological remodeling of the endplate region--were identified. Studies of neuromuscular transmission in this model system provide an excellent opportunity to evaluate the role of AChE without complications arising from use of inhibitors.
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PMID:Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice. 1531 43

Phenthonium (Phen), a quaternary analog of hyoscyamine, is a blocker of muscarinic activity and an allosteric blocker of alpha(1)2betagammaepsilon nicotinic receptors. Specifically, Phenthonium increases the spontaneous release of acetylcholine at the motor endplate without depolarizing the muscle or inhibiting cholinesterase activity. This paper compares Phenthonium's effects on sympathetic transmission and on ganglionic nicotinic receptor activation. Neurotransmitter release and twitch of the rat vas deferens were induced either by electrical stimulation or by 1,1-dimethyl-4-phenylpiperazine (DMPP) activation of nicotinic receptors. Contractions independent of transmitter release were induced by noradrenaline and adenosine 5'-triphosphate (ATP). Phenthonium inhibited transmitter release and depressed twitch without changing the responsiveness to noradrenaline or ATP. Twitch depression did not occur after K(+)-channel blockade with 4-aminopyridine (4-AP) or charybdotoxin. DMPP had a similar effect, but high concentrations induced contraction of non-stimulated organs. Incubation of Phenthonium inhibited further DMPP twitch depression and non-competitively depressed the contractile responses elicited by DMPP. Furthermore, mecamylamine, but neither methyllycaconitine nor atropine, blocked the contraction elicited by DMPP. Phenthonium and DMPP are K(+)-channel openers that primarily inhibit sympathetic transmission. Contraction induced by DMPP was probably mediated by neuronal nicotinic receptor other than the alpha7 subtype. The blockade of DMPP contractile response was unrelated to Phenthonium's antimuscarinic or K(+)-channel opening activities. Since Phenthonium's quaternary chemical structure limits its membrane diffusion, the non-competitive inhibition of DMPP excitatory responses should be linked to allosteric interaction with neuronal nicotinic receptors that putatively qualify Phenthonium as a novel modulator of cholinergic synapses.
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PMID:Allosteric interaction of the anticholinergic drug [N-(4-phenyl)-phenacyl-l-hyoscyamine] (Phenthonium) with nicotinic receptors of post-ganglionic sympathetic neurons of the rat vas deferens. 1954 Feb 21

Rivastigmine is a non-competitive reversible inhibitor of acetylcholinesterase which is approved as one of the fi rst-line treatment options for Alzheimer's disease. We present the case of a 33-year-old woman with acute cholinergic syndrome secondary to deliberate rivastigmine poisoning. The patient presented at the emergency department (ED) with drowsy consciousness, dizziness, vomiting, diarrhea, sweating, and hypertension (171/103 mmHg). At the scene, an empty bottle of Rivast 120 mL/Bot, containing rivastigmine 2 mg/mL, was found beside the patient. Two hours later, we noted bronchorrhea and persistent salivation along with drowsiness, agitation, fatigue, incontinence, and limbs paralysis. A notably low serum cholinesterase level (651 U/l) was identified. Acute cholinergic syndrome secondary to rivastigmine intoxication was diagnosed. Endotracheal intubation with ventilator support was required due to respiratory failure. Atropine (0.5 mg intravenous injection) was administered. She was subsequently admitted to the intensive care unit for further care. Extubation was performed on the third day. The patient insisted on being discharged on the second day after extubation, and after administration of a total of 11 mg of atropine, no signs of either intermediate syndrome or delayed polyneuropathywere noted. rivastigmine, an acetylcholinesterase inhibitor, can precipitate an acute cholinergic crisis in cases of intoxication. Typical clinical features of cholinergic excess include increased secretions in the airway and oral cavity, miosis, diarrhea, anxiety, twitching, bronchoconstriction, convulsions, confusion, and gastrointestinal and muscular cramps. The treatment for acute cholinergic crisis is administration of atropine alone or in combination with an antidote to the cholinesterase inhibitor (such as pralidoxime). Patients often recover well with atropine supplements and optimal supportive care.
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PMID:Successful Resuscitation of a Young Girl Who Drank Rivastigmine With Respiratory Failure. 3299 49