Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The susceptibility to competitive ganglionic blocking agents such as hexamethonium (C6), tetraethylammonium bromide (TEAB), mecamylamine and d-tubocurarine (d-TC), of the superior cervical ganglion in cats with pancreatectomy and spontaneous diabetes or in animals treated with contrainsular drugs such as cortisone or dihydrochlorothiazide, was found to be decreased as compared to the reactivity of normal controls. The increased tolerance to ganglioplegics was not correlated with the elevation of the blood sugar level, and proved to be resistant to an acute administration of insulin. The results could not be explained by a decrease in the specific cholinesterase activity of the ganglionic tissue due to diabetes. Alteration of the peripheral autonomic synaptic transmission may be an early sign of diabetic neuropathy.
...
PMID:Diabetes-induced alterations of autonomic nerve function in the cat. 3 32

We present 3 patients with chronic renal failure who had postoperative paralysis due to the administration muscle relaxants. One of them received gallamine, a non-depolarizing blocking agent that is mainly excreted by the kidney (70--90%). Two of them received pancuronium bromide, also a non-depolarizing blocking agent which is partially excreted by the kidneys (37--44%). All of them received succinylcholine. Succinylcholine is hydrolyzed by the serum cholinesterase into succinylmonocholine and choline. These active metabolites are excreted by the kidney. These patients serve as examples of the importance of considering the route of excretion of drugs and their metabolites in clinical situations involving the renal failure patient. The pharmacology of drugs administered relative to surgical procedures is reviewed.
...
PMID:Anesthesia related muscle paralysis in renal failure. 35 7

The acetylcholinesterase was purified by CM-Sephadex chromatography and affinity chromatography on Sepharose bound m-[6-(6-aminocaproylamino)caproylamino]phenyltrimethylammonium bromide. The purified enzyme was obtained with a specific activity of 5470 U/mg (1160-fold purification) and a 89% yield. The molecular weight of the native enzyme was estimated to be 144,000. The enzyme is split into two subunits of approximately equal molecular weight (Mr 69,000) by SDS treatment. It is a glycoprotein and can be resolved by disc gel electrophoresis into seven and by isoelectric focusing into more than ten multiple forms. The N-terminal amino acid is serine.
...
PMID:[Purification by affinity chromatography and properties of the acetylcholinesterase of formosan cobra (Naja naja atra) venom (author's transl)]. 53 51

A case report of a 22-year-old patient with accommodative paralysis is presented including (1) the five-year history beginning with infectious mononucleosis; (2) recent clinical examination showing accomodative paralysis and reduced pupilary responses to light and near; (3) objective recordings confirming both the absence of any accommodation and the presence of pupillary responses to monocular and binocular near stimuli and to light, the latter with pupillary escape; and finally (4) neuropharmacological tests showing 7-diopter accommodative responses to pilocarpine (an acetylcholine substitute acting directly on the ciliary muscle receptor sites) and absent responses to demecarium bromide (a cholinesterase blocking agent which potentiates neurally released acetylcholine). Infectious mononucleosis includes ocular signs and symptoms. In young persons with accommodative difficulties, infectious mononucleosis should be suspected.
...
PMID:Paralysis of accommodation in infectious mononucleosis. 55 29

Acetylcholinesterase from pig cerebral cortex was solubilised with 1% (w/v) Triton X-100 and purified by affinity chromatography. Three different ligands were investigated and details are given for their preparation. The elution profile depended on the presence of Triton X-100, the ionic strength and the inhibitor used to remove the enzyme from the column as well as the nature of the affinity material. The most efficient purification was obtained when the enzyme was eluted from a column containing the acetylcholinesterase inhibitor [1-methyl-9-(Nbeta-epsilon-amino-caproyl)-beta-aminopropylamino] acridinium bromide hydrobromide covalently linked to Sepharose 4B. A recovery of 44% of the applied enzyme was eluted from the column with a specific activity of 148 mumoles min-1 mg-1 and a purification of 900-fold.
...
PMID:Purification of acetylcholinesterase from pig cerebral cortex by affinity chromatography. 70 39

A 73-year-old white woman with bilateral congenital mydriasis had no other obvious abnormalities. The pupils reacted almost imperceptibly to light. There was no detectable reaction to accommodation and convergence. Pupillary response to pilocarpine 4% solution indicated the presence of the sphincter muscle. However, the failure of the pupil to react to a potent cholinesterase inhibitor (demecarium bromide 0.25%) suggested an abnormality relative to acetylcholine production in the iris. Rapid and marked pupillary response to phenylephrine 10% solution indicated the presence of the dilator muscle. Analysis of the family history with eight known cases of bilateral congenital mydriasis occurring only in females suggested that the mechanism of inheritance is most probably autosomal dominant. A degree of sex limitation cannot be absolutely excluded.
...
PMID:Bilateral congenital mydriasis. 94 37

Out of 12 oximes and amidoximes (3 of which were new to the literature) the following showed a distinct antilethal effect in DFP poisoning: RA14 (1-methylbenzimidazole-2-aldoxime methiodide), RA14 (pyridine-4-aldoxime dodecyl bromide), and RA24 (pyridine-2-aldoxime dodecyl bromide). These compounds also reactivated acetylcholinesterase (AChE) in vitro, but had no effect on this enzyme in vivo. Moreover, addition of the dodecyl chain to pyridinealdoxtimes, or in a less degree replacement of the pyridine ring with benzimidazole in aldoximes, distinctly increased acute toxicity and lipophilicity when compared with the parent pyridine compounds, along with protective action in DFP poisoning.
...
PMID:Potential acetylcholinesterase reactivators: oxime and amidoxime derivatives. 101 93

7-Bromo-(3a,5-cis)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-pyrrolo[2,3- 6]indol-5-ol fumarate (HP 736) is a novel opioid analgesic. In vitro, HP 736 displaces [3H]dihydromorphine (IC50 = 8.3 x 10(-10) M) and [3H]bremazocine (IC50 = 7.4 x 10(-8) M) from mu and kappa opioid receptors, respectively, and displays modest acetylcholinesterase inhibitory activity (IC50 = 4.0 x 10(-5) M). The in vivo antinociceptive activity of HP 736 was found to be comparable to morphine in the modified Haffner's tail clip assay in mice and the D'Amour-Smith tail flick assay in rats. Moreover, these analgesic effects were found to be completely antagonized by the administration of the narcotic antagonist naloxone. A major liability of opioid analgesics such as morphine is the potential to cause cardiorespiratory depression. HP 736 (2, 4 and 10 mg/kg, i.v.) was found to cause significantly less respiratory depression in the anesthetized dog when compared to equivalent doses of morphine. At 10 mg/kg, morphine caused a 48% reduction in arterial oxygen partial pressure (PaO2) (-42.3 +/- 2.5 mm Hg) and a 52% increase in arterial carbon dioxide partial pressure (PaCO2) (21.0 +/- 3.4 mm Hg). In contrast, the same dose of HP 736 produced no significant decrease in PaO2, but did cause a slight 19% increase in PaCO2 (8.2 +/- 1.3 mm Hg), which was significantly less than the response seen after morphine treatment. It was found that pretreatment of the dogs with atropine sulfate (1 mg/kg, i.v.) "unmasked" the respiratory depressant activity of HP 736 (2 mg/kg, i.v.), indicating that the acetylcholinesterase inhibitory activity of the compound may contribute to its reduced cardiorespiratory liability. Finally, in confirmatory experiments conducted in conscious goats, HP 736 (0.5 mg/kg, i.v.) was found to stimulate pulmonary ventilation, increase PaO2 and oxygen consumption (+40%) and decrease PaCO2 with an overall stimulatory effect on the metabolic rate. In contrast, the same dose of morphine decreased metabolic rate, reduced pulmonary ventilation (-20%) and PaO2 and increased PaCO2. Overall, the results of these studies indicate that HP 736 is a potent opioid analgesic which appears to lack significant cardiorespiratory depressant activity.
...
PMID:Cardiorespiratory effects of the novel opioid analgesic HP 736 in the anesthetized dog and conscious goat. 134 66

Dopamine (DA)-containing neurons in primary dissociated cell cultures derived from the embryonic mouse mesencephalon (day E13) were studied by histochemical and electrophysiological techniques. DA neurons exhibited two distinct morphologies, fusiform and multipolar, tended to reside in groups and organize dendrites into common fascicles. While these neurons expressed the cell-surface marker acetylcholinesterase, the presence of this enzyme could not be used to identify DA neurons unequivocally, since it was also observed in nondopaminergic cells. Neurons were therefore identified as DA by their distinct morphology, and this identification was validated with a double-labeling procedure that entailed the intracellular deposition of a fluorescent dye (Lucifer yellow or ethidium bromide), followed by processing for tyrosine hydroxylase immunocytochemistry. DA neurons identified in this manner were observed to have resting membrane potentials between -50 and -75 mV, input resistances of 50-360 M omega, and membrane time constants of 4.1-14.1 msec. Forty-seven percent of these cells displayed spontaneous activity that was irregular in nature and often contained bursts (burst length was between two and six action potentials). The DA neurons displayed a variety of ionic conductances, including (1) a Na+ conductance (gNa) that underlies the action potential, (2) Ca2+ conductances (gCa) that mediate the nonsomatic low- and high-threshold spikes observed, and (3) at least three K+ conductances (gK). Voltage-clamp analysis revealed several distinct transmembrane ionic currents, including (1) a large, rapidly inactivating tetrodotoxin-sensitive inward Na+ current (INa), (2) a 4-aminopyridine-sensitive, transient early outward K+ current that required a conditioning hyperpolarization of the membrane to be activated by a subsequent depolarization (A-current, IA), (3) a slowly developing inward current that was seen only after a conditioning hyperpolarization of the membrane and that was dependent on the presence of external Ca2+ ions (ICa), and (4) a late-onset, noninactivating K+ current. Between 25% and 54% of the late-onset K+ current was Ca(2+)-dependent and was not affected by tetraethylammonium ions. This current was termed IAHP. The remaining current was not sensitive to changes in the extracellular Ca2+ concentration but was blocked by external tetraethylammonium. This current was termed IK. The direct pressure application of DA (1-200 microM) onto the soma dose-dependently hyperpolarized these neurons; this effect was potentiated by the presence of the catecholamine reuptake blocker cocaine hydrochloride (10-200 microM). Under voltage-clamp conditions, DA was observed to increase IK significantly and had little effect on IAHP.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Membrane properties of identified mesencephalic dopamine neurons in primary dissociated cell culture. 135 96

Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the established agents atracurium besilate and vecuronium bromide. Pipecuronium and Org 9426 are steroidal compounds, the latter being a monoquaternary agent, whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium compounds. Pipecuronium and doxacurium have a relatively slow onset and a long duration of action. Pipecuronium produces maximum block in 3 to 6 min when given in a dose of 45 to 80 micrograms/kg, and a duration of clinical relaxation of between 40 and 110 min. Doxacurium is more potent, but is the least rapid and the longest acting relaxant currently available. When administered in doses of 37 to 80 micrograms/kg, it produces maximum block within 3.5 to 10 min, with a duration of clinical relaxation of 77 to 164 min. The advantage of both pipecuronium and doxacurium is their cardiovascular stability. Both agents are primarily eliminated via the kidneys and both have now been licensed for use in the US. Mivacurium is a muscle relaxant with a short duration of action. When administered in doses of 0.1 to 0.25 mg/kg it produces maximum block in 2 to 4 min, but the duration of clinical relaxation is less than 20 min. Higher doses which could induce a faster neuromuscular block are unfortunately associated with some histamine liberation. The drug is metabolised by plasma cholinesterase. Mivacurium has also been licensed for use in the US. Org 9426 is an agent with a rapid onset but an intermediate duration of action. A dose of 0.5 to 0.6 mg/kg induces maximum block in about 1.5 min and has a duration of clinical relaxation of about 30 min. The rapid onset of effect could be useful for early intubation as an alternative to suxamethonium chloride. However, much more clinical experience is needed with this agent, particularly with regard to duration of action of larger doses and occurrence of side effects. The drug is mainly eliminated via the liver.
...
PMID:Newer neuromuscular blocking drugs. An overview of their clinical pharmacology and therapeutic use. 138 13


1 2 3 4 5 6 7 8 9 10 Next >>

---