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

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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)

Studies have been made on the interaction of several groups of quartenary ammonium salts with cholinoreceptors of m. rectus abdominis of the frog Rana temporaria, and isolated m. retractor infundibuli of the octopus Todarodes pacificus, as well as with cholinesterases of the frog brain and visual ganglia of the octopus. The derivatives of polymethylene bis(trimethylammonium) compounds, being cholinomimetic drugs for frog muscle, do not exert cholinomimetic influence on octopus muscle. The same difference with respect to their effect on frog and octopus receptors was found in anabazin derivatives. Among amide derivatives of acetylcholine, the strongest mimetic effect on cholinoreceptors of both animals was exhibited by a piperazine isolog with gauche-conformation, whereas N-methyl isolog with trans-conformation was found to be the strongest inhibitor of cholinesterases. Cholinoreceptors and cholinesterase of the octopus were less sensitive to the effect of the investigated quartenary ammonium salts than those of the frog.
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PMID:[Comparison of the cholinoreceptor and cholinesterase properties of the frog Rana temporaria and the squid Todarodes pacificus]. 315 37

Adult Ascaridia galli and Heterakis gallinae obtained from the fowl (Gallus gallus) were treated in vitro with 10(-2) to 10(-5) M parbendazole and piperazine adipate for 10-60 min at 38 degrees C. Both the compounds at 10(-2) M caused mortality of A. galli and H. gallinae after a maximum of 30 min exposure. The effect of the drugs on the homogenates of the treated worm was investigated. Parbendazole (10(-2) M) inhibited malate oxidation by 68% in A. galli and 62% in H. gallinae. Piperazine adipate (10(-2) M) inhibited malate oxidation by 78% in both parasites. In A. galli oxaloacetate reduction was inhibited by 41 and 26% by 10(-2) M parbendazole and piperazine adipate, respectively; with H. gallinae this inhibition was found to be 39 and 55%, respectively. Aldolase activity in both the parasites was also inhibited by 10(-2) M parbendazole and piperazine adipate. Both compounds caused an inhibition of acid phosphomonoesterase activity, but the activities of lactate dehydrogenase and alkaline phosphomonoesterase were not affected significantly. Parbendazole (10(-2) M) had no significant effect on the cholinesterase activity of these parasites, but piperazine adipate (10(-2) M) caused an inhibition of 96% in A. galli and 93% in H. gallinae. The possible mode of action of the drugs is discussed.
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PMID:Effect of parbendazole and piperazine adipate on the activity of some enzymes of Ascaridia galli and Heterakis gallinae. 361 27

Latency to vocalization and jump/flinch behaviors were scored as the nociceptive endpoints in mice in a grid-shock apparatus that delivered increasing shock levels through a grid floor. Morphine produced a dose-dependent increase in latency to vocalization and was equieffective at a 70- or 80-dB vocalization level. The jump/flinch behavior was not dose dependently modified by morphine. The mouse grid-shock procedure was pharmacologically characterized by using the 70-dB level endpoint. The antinociceptive potencies of the mu opioid receptor agonist analgesics, morphine, methadone, fentanyl, oxycodone, meperidine, etorphine and codeine, correlated well (R = .989) with their clinical doses. The mixed opioid agonist-antagonist, pentazocine, and the partial mu receptor opioid agonist, buprenorphine, were partially effective. The alpha-2 adrenergic agonists clonidine and flupirtine and the serotonergic 5-HT1B agonists 1-(m-trifluoromethyl)piperazine and anpirtoline, were all effective antinociceptives with potencies 20 times less to one-half that of morphine. The gamma-aminobutyric acid agonist 4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3(2H)-one was partially effective, whereas the gamma-aminobutyric acid uptake inhibitors SKF 100300A [N-(4,4-diphenyl-3-butenyl)-guvacine] and tiagabine were highly effective and 6 and 2 times less potent than morphine, respectively. The muscarinic agonists, oxotremorine and arecoline, and the cholinesterase inhibitor, physostigmine, were also antinociceptive, ranging from 7 times less to 100 times more potent than morphine. The nonsteroidal anti-inflammatory analgesic, aspirin, was inactive. The present studies show that the latency to a defined level of vocalization as the nociceptive endpoint provides a reliable, highly reproducible and high through-put test for antinociception in nonrestrained mice.
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PMID:The mouse grid-shock analgesia test: pharmacological characterization of latency to vocalization threshold as an index of antinociception. 801 47

Our previous studies demonstrated that FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various rodent models of amnesia, through activation of the somatostatin neuronal system. To extend the antiamnesic action of FK960 to nonhuman primates, FK960 was evaluated for its ability to reverse the deficits in visual recognition memory produced by muscarinic cholinergic receptor blockade by scopolamine or N-methyl-D-aspartate receptor blockade by dizocilpine (MK-801) in four rhesus monkeys performing a computer-automated version of delayed nonmatching to sample, with a list length of 20 trial-unique graphic symbols. Furthermore, the effects of FK960 were compared with those of physostigmine, a cholinesterase inhibitor. Doses of FK960 (1, 3.2, 10, 32,100, 320 or 1000 microg/kg) injected i.m. 30 min before testing minimally affected visual recognition memory when administered alone. FK960 (1, 3.2, 10 or 32 microg/kg) significantly antagonized the deficits in visual recognition memory produced by scopolamine (10 microg/kg); the same doses of the drug minimally affected the deficits produced by dizocilpine (32 microg/kg). Similarly, physostigmine (3.2, 10 or 32 microg/kg) significantly and dose-dependently restored the visual recognition memory deficits produced by scopolamine (10 microg/kg) but not those produced by dizocilpine (32 microg/kg). From these results, we conclude that FK960 improves deficits in recognition memory associated with central cholinergic hypofunction in nonhuman primates, and we suggest that the therapeutic potential of this drug for patients with dementia should be evaluated.
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PMID:FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine. 906 4

Modes of action of anthelmintic drugs are described. Some anthelmintic drugs act rapidly and selectively on neuromuscular transmission of nematodes. Levamisole, pyrantel and morantel are agonists at nicotinic acetylcholine receptors of nematode muscle and cause spastic paralysis. Dichlorvos and haloxon are organophosphorus cholinesterase antagonists. Piperazine is a GABA (gamma-amino-butyric acid) agonist at receptors on nematode muscles and causes flaccid paralysis. The avermectins increase the opening of glutamate-gated chloride (GluCl) channels and produce paralysis of pharyngeal pumping. Praziquantel has a selective effect on the tegument of trematodes and increases permeability of calcium. Other anthelmintics have a biochemical mode of action. The benzimidazole drugs bind selectively to beta-tubulin of nematodes, cestodes and fluke, and inhibit microtubule formation. The salicylanilides: rafoxanide, oxyclozanide, brotianide and closantel and the substituted phenol, nitroxynil, are proton ionophores. Clorsulon is a selective antagonist of fluke phosphoglycerate kinase and mutase. Diethylcarbamazine blocks host, and possibly parasite, enzymes involved in arachidonic acid metabolism, and enhances the innate, nonspecific immune system.
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PMID:Modes of action of anthelmintic drugs. 926 48

The effect on memory processes of modulation of 5-HT1A receptor subtype was investigated in the mouse passive avoidance test. The administration of 5-HT1A-receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-2-phthalimmido)butyl]piperazine) and WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide) produced a dose-dependent amnesic effect comparable to that obtained with the well-known amnesic agents scopolamine and dicyclomine. Pretreatment with the 5-HT1A-receptor agonists 8-OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin) and 5-CT (5-carboxamidotryptamine) dose-dependently prevented the amnesia induced by 5-HT1A antagonists, scopolamine, dicyclomine and exposure to an hypoxic environment. The antiamnesic effect exerted by 5-HT1A-receptor agonists was comparable to that produced by the nootropic drug piracetam and cholinesterase inhibitor physostigmine. At effective doses, neither 5-HT1A-receptor agonists nor 5-HT1A-receptor antagonists produced any impairment of mouse motor coordination (rota-rod test), spontaneous motility (Animex apparatus) and inspection activity (hole board). These results indicate that modulation of 5-HT1A-receptors appears to play an important role in the regulation of cognitive processes.
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PMID:Role of 5-HT1A receptors in a mouse passive avoidance paradigm. 1120 14

The cholinergic hypothesis of Alzheimer's disease (AD) has spurred the development of numerous structural classes of compounds with different pharmacological profile aimed at increasing central cholinergic neurotransmission. Thus proving a symptomatic treatment for this disease are cholinomimetics with the pharmacological profile of acetyl cholinesterase (AchE) inhibitors. The novel bioactive 1-[bis(4-fluorophenyl)-methyl]piperazine derivatives were synthesized under mild conditions using different aryl/alkyl halides and heterocyclic alkyl halides with 1-[bis(4-fluorophenyl)-methyl]piperazine in the presence of powdered potassium carbonate in N,N-dimethylformamide. All the synthesized compounds were characterized by spectroscopic techniques, elemental analysis and were screened for their efficacy as AchE inhibitor. Some derivatives in this class showed good inhibition against AchE as compared to neostigmine as standard.
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PMID:Synthesis and efficacy of 1-[bis(4-fluorophenyl)-methyl]piperazine derivatives for acetylcholinesterase inhibition, as a stimulant of central cholinergic neurotransmission in Alzheimer's disease. 1673 18

Amyloid-beta-induced neuroinflammation plays a central role in the extensive loss of cholinergic neurons and cognitive decline in Alzheimer's disease. The acetylcholinesterase (AChE) inhibitors are the first class of drugs used to enhance surviving cholinergic activities. However, their limited effectiveness following long-term treatment raises a need for new multi-target therapies. We report herein a novel piperazine derivative compound PMS1339 possesses multifunctional properties including anti-platelet-activating factor, AChE inhibition, Abeta aggregation inhibition and cognitive improvement. PMS1339 could significantly inhibit both mice brain AChE (IC50=4.41+/-0.63 microM) and sera butyrylcholinesterase (BuChE, IC50=1.09+/-0.20 microM). PMS1339 was also found to inhibit neuronal AChE secreted by SH-SY5Y cell line (IC50=17.95+/-2.31 microM). Enzyme kinetics experiments performed on electric eel AChE indicated that PMS1339 acts as a mixed type competitive AChE inhibitor. Molecular docking studies using the X-ray crystal structure of AChE from Torpedo californica elucidated the interactions between PMS1339 and AChE: PMS1339 is well buried inside the active-site gorge of AChE interacting with Trp84 at the bottom, Tyr121 halfway down and Trp279 at the peripheral anionic site (PAS). Thioflavin T-based fluorimetric assay revealed the ability of PMS1339 to inhibit AChE-induced Abeta aggregation. In-vivo study indicated PMS1339 (1 mg/kg i.p.) reversed scopolamine-induced memory impairment in mice. Overall, these findings indicated that PMS1339 exhibits tri-functional properties in vitro and cognitive improvement in vivo, and revealed the emergence of a multi-target-directed ligand to tackle the determinants of Alzheimer's disease.
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PMID:Novel piperazine derivative PMS1339 exhibits tri-functional properties and cognitive improvement in mice. 1946 Jan 90

The 5-hydroxytryptamine system is thought to play a crucial role in the pathophysiology of depression and represents the target for selective 5-HT reuptake inhibitors (SSRIs). Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were bred from Sprague-Dawley (SPD) rats to produce strains with increased (FSL) or decreased (FRL) sensitivity to the cholinesterase inhibitor. The FSL rats have been identified as a good model of depression. Many studies in normal rats showed that chronic treatments with SSRIs reduce the densities of SERT. The objective of the present investigation was to assess the influence of chronic fluoxetine treatment on SERT density (Bmax; fmol/mg) in the FSL rat model of depression, relative to that in the FRL rats and SPD rats. FSL, FRL and SPD rats were randomly assigned into groups receiving the vehicle or 10 mg/kg of fluoxetine i.p. for 14 days. Binding was assessed by incubating the brain sections in a buffer containing 20 pM of [(125)I]-RTI-55 [[(125)I](-)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane and 200 nM of GBR12935 [1-(2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine]. The fluoxetine treatment reduced B(max) in all three rat strains when the saline and respective fluoxetine groups were compared (e.g., the FSL-SAL relative to FSL-FLX groups). Chronic fluoxetine treatment reduces the densities of SERT in the FSL rats to a larger extent than in the normal SPD control rats.
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PMID:Chronic fluoxetine treatment has a larger effect on the density of a serotonin transporter in the Flinders Sensitive Line (FSL) rat model of depression than in normal rats. 1992 93

In the current study, some novel ethyl 6- [(substituted-phenylpiperazine]-3(2H)-pyridazinone-2-yl propionate III and 6-[(substituted-phenylpiperazine]-3(2H)-pyridazinone-2-yl propionohydrazide IV derivatives were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. 6-Substituted-3(2H)-pyridazinone-2-yl propionate IIIa-e derivatives showed significant inhibitory activity against AChE and BChE. 6-[4-(3-Trifluoromethylphenyl)piperazine]-3(2H)-pyridazinone-2-yl propionate IIIe has been found to be the most active compound in terms of inhibition of either AChE or BChE. Compound IIIe exhibited inhibitory activity close to that of galantamine (CAS 357-70-0) and did not show any selectivity between the two enzymes. Also the antimicrobial activities of III and IV derivatives have been evaluated. All III and IV derivatives exhibited poor antibacterial activities but moderate antifungal activities.
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PMID:Synthesis and antimicrobial, acetylcholinesterase and butyrylcholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(2H)-pyridazinone. 2071 36


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