Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of treatment with the medicinal plant Rhayva stricta Decne, on monoamine oxidase (MAO) and cholinesterase activity, and on the concentration of brain biogenic amines was studied in rats. R. stricta extract, at doses of 0.2 and 0.5 g kg(-1), significantly (P < 0.05-0.01) increased the hepatic and cerebral activity of MAO by 36-127%. The higher doses used (2.0 and 8.0 g kg(-1)) produced smaller (10-26%) and statistically insignificant increases in MAO activity in liver and brain. Cholinesterase activity in blood, liver and brain was not significantly influenced by treatment with R. stricta. The concentrations of the measured biogenic amines (noradrenaline, adrenaline, 5-hydroxytryptamine and dopamine) were significantly lowered in rats treated with R. stricta. The observed increase in MAO activity may be responsible for the lowered biogenic amines levels and may, in part, be responsible for the pharmacological effects of R. stricta extract in rats.
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PMID:Effect of Rhazya stricta Decne on monoamine oxidase and cholinesterase activity and brain biogenic amine levels in rats. 1109 75

Inspite of large number of studies on the neurochemical changes in the stress, an equivocal case is yet to be made for the role of a specific neurotransmitter in this important neurobiological disorder. The difficulty arises from the fact that there is no single neurotransmitter system appears to be responsible for the stress induced damage to the hippocampal neurons. The present study evaluates the effect of restraint stress on the alterations in the levels of biogenic amines, aminoacids and acetylcholinesterase activity in the hippocampus. Male Wistar rats of 45 days old were subjected to 6 hours of daily restraint stress over a period of 21 days. Immediately after the last session of stress, rats were sacrificed and neurotransmitter levels were estimated in the hippocampus. A significant (p < 0.001) decrease in the levels of noradrenaline, dopamine, 5-hydroxytryptamine and acetylcholinesterase activity in the stressed rats was observed compared to controls. However, levels of glutamate was significantly (p < 0.001) increased in stressed rats. These results indicate that chronic restraint stress decreases aminergic and cholinergic neurotransmission, and increases the glutamatergic transmission in the hippocampus.
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PMID:Restraint stress-induced alterations in the levels of biogenic amines, amino acids, and AChE activity in the hippocampus. 1115 83

Acute colonic pseudo-obstruction (Ogilvie's syndrome) can be defined as a clinical condition with symptoms, signs and radiological appearance of acute large bowel obstruction unrelated to any mechanical cause. Recent reports of the efficacy of cholinesterase inhibitors in relieving acute colonic pseudo-obstruction have fuelled interest in the pharmacological treatment of this condition. The aim of the present review is to outline current perspectives in the pharmacological treatment of patients with acute colonic pseudo-obstruction. The best documented pharmacological treatment of Ogilvie's syndrome is intravenous neostigmine (2-2.5 mg), which leads to quick decompression in a significant proportion of patients after a single infusion. However, the search for new colokinetic agents for the treatment of lower gut motor disorders has made available a number of drugs that may also be therapeutic options for Ogilvie's syndrome. Among these agents, the potential of 5-hydroxytryptamine-4 receptor agonists and motilin receptor agonists is discussed.
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PMID:Review article: the pharmacological treatment of acute colonic pseudo-obstruction. 1168 85

The organophosphate insecticide chlorpyrifos and the carbamate insecticide carbaryl were investigated in adult male rats in terms of their effects on the activity of brain monoamine oxidase-A (MAO-A) activity and on the platelet uptake of 5-hydroxytryptamine (5-HT). The activities of brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) were also determined. For each compound two different dosage regimens were employed. In the acute study, chlorpyrifos or carbaryl was administered at a single intraperitoneal dose of 100 mg/kg or 50 mg/kg, respectively In the subacute study, chlorpyrifos was injected at a daily dose of 20 mg/kg for 7 days, while carbaryl was given at a daily dose of 10 mg/kg for 14 days. Acute chlorpyrifos administration produced a 85.01% inhibition of AChE and a 43.4% inhibition of BuChE but had no effect on MAO-A activity and 5-HT uptake. In contrast, subacute chlorpyrifos exposure caused a 94.96% inhibition of AChE and a 85.8% inhibition of BuChE and, also, elicited a significant (35.02%) reduction in the platelet uptake of 5-HT. MAO-A activity was not affected. Acute carbaryl administration produced a 56.38% AChE inhibition and a 55.95% BuChE inhibition and also caused a significant (26.36%) decrease in 5-HT uptake but no change in MAO-A. Subacute carbaryl exposure failed to affect significantly any of the biochemical parameters determined. Interference with the 5-HT system by chlorpyrifos and carbaryl could contribute to the toxicity of these pesticides.
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PMID:Inhibition of rat platelet 5-hydroxytryptamine uptake by chlorpyrifos and carbaryl. 1188 70

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the emerging notion that 5-HT plays a key role on memory formation.
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PMID:Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task. 1203 33

CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor of AChE, it is 115 times more potent against this enzyme than against butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition of central (brain) AChE than peripheral (heart) AChE. In vivo CHF2819, 0.5, 1.5, and 4.5 mg/kg p.o., significantly and in dose-dependent manner increased acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging animals, with lower basal ACh levels than young adult rats, also exhibit a marked increase in hippocampal levels of this neurotransmitter after administration of CHF2819. At 1.5 mg/kg p.o. CHF2819 attenuated scopolamine-induced amnesia in a passive avoidance task. Furthermore, it decreased dopamine (DA) levels and increased extracellular levels of 5-hydroxytryptamine (5-HT) in the hippocampus, without modifying norepinephrine (NE) levels. By oral administration to young adult rats CHF2819 did not affect extracellular hippocampal levels of glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine (Tau), arginine (Arg) or citrulline (Cit). Functional observational battery (FOB) screening demonstrated that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological endpoints (body weight and temperature). CHF2819 induced, however, involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a dose-dependent manner. The neurochemical and behavioral profiles of CHF2819 suggest that this orally active novel AChEI could be of clinical interest for the treatment of Alzheimer-type dementia associated with multiple neurotransmitter abnormalities in the brain. In particular, CHF2819 might be a useful therapeutic drug for AD patients with cognitive impairment accompanied by depression.
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PMID:CHF2819: pharmacological profile of a novel acetylcholinesterase inhibitor. 1207 May 26

SL65.0155 [5-(8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-[1-(2-phenyl ethyl)-4-piperidinyl]-1,3,4-oxadiazol-2(3H)-one monohydrochloride] is a novel benzodioxanoxadiazolone compound with high affinity for human 5-hydroxytryptamine (5-HT)(4) receptors (K(i) of 0.6 nM) and good selectivity (greater than 100-fold for all other receptors tested). In cells expressing the 5-HT(4(b)) and 5-HT(4(e)) splice variants, SL65.0155 acted as a partial agonist, stimulating cAMP production with a maximal effect of 40 to 50% of serotonin. However, in the rat esophagus preparation, SL65.0155 acted as a 5-HT(4) antagonist with a pK(b) of 8.81. In addition, SL65.0155 potently improved performance in several tests of learning and memory. In the object recognition task, it improved retention at 24 h when administered i.p. or p.o. (0.001-0.1 mg/kg). This effect was antagonized by the 5-HT(4) antagonist SDZ 205,557, itself without effect, demonstrating that the promnesic effects of SL65.0155 are mediated by 5-HT(4) agonism. SL65.0155 also reversed the cognitive deficits of aged rats in the linear maze task and the scopolamine-induced deficit of mice in the water maze task. Furthermore, the combined administration of an inactive dose of SL65.0155 with the cholinesterase inhibitor rivastigmine resulted in a significant promnesic effect, suggesting a synergistic interaction. SL65.0155 was devoid of unwanted cardiovascular, gastrointestinal, or central nervous system effects with doses up to more than 100-fold higher than those active in the cognitive tests. These results characterize SL65.0155 as a novel promnesic agent acting via 5-HT(4) receptors, with an excellent preclinical profile. Its broad range of activity in cognitive tests and synergism with cholinesterase inhibitors suggest that SL65.0155 represents a promising new agent for the treatment of dementia.
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PMID:SL65.0155, a novel 5-hydroxytryptamine(4) receptor partial agonist with potent cognition-enhancing properties. 1213 Jul 38

1 This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT) and to characterize the 5-HT receptors involved in 5-HT responses in the pig intravesical ureter. 2 5-HT (0.01-10 microM) concentration-dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration-independent. The 5-HT(2) receptor agonist alpha-methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained with 5-CT, 8-OH-DPAT, m-chlorophenylbiguanide and RS 67333, 5-HT(1), 5-HT(1A), 5-HT(3) and 5-HT(4) receptor agonists, respectively. 5-HT did not induce relaxation of U46619-contracted ureteral preparations. Pargyline (100 microM), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration-response curves for 5-HT. 3 5-HT-induced tone was reduced by the 5-HT(2) and 5-HT(2A) receptor antagonists ritanserine (0.1 microM) and spiperone (0.2 microM), respectively. However, 5-HT contraction was not antagonized by cyanopindolol (2 microM), SDZ-SER 082 (1 microM), Y-25130 (1 microM) and GR 113808 (0.1 microM), which are respectively, 5-HT(1A/1B), 5-HT(2B/2C), 5-HT(3), and 5-HT(4) selective receptor antagonists. 4 Removal of the urothelium did not modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium channels, alpha-adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 microM), phentolamine (0.3 microM) and guanethidine (10 microM), respectively, reduced the contractions to 5-HT. However, physostigmine (1 microM), atropine (0.1 microM) and suramin (30 microM), inhibitors of cholinesterase activity, muscarinic- and purinergic P(2)-receptors, respectively, failed to modify the contractions to 5-HT. 5 These results suggest that 5-HT increases the tone of the pig intravesical ureter through 5-HT(2A) receptors located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated via noradrenaline release from sympathetic nerves.
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PMID:Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter. 1252 83

The present study was designed to investigate whether a combination of a new acetylcholinesterase inhibitor we have synthesized, galanthaminium bromide, and an agonist of 5-hydroxytryptamine(4) receptors, RS 67333, at doses ineffective alone, improves performance in tasks involving place and object recognition memory. Dose responses of each compound were determined in order to select doses without effect alone. Accordingly, young adult rats were injected intraperitoneally with galanthaminium bromide (0.3 mg/kg)+RS 67333 (0.01 mg/kg), and old rats with galanthaminium bromide (0.1 mg/kg for place and 0.3 mg/kg for object recognition)+RS 67333 (1 mg/kg). Drugs were injected before the acquisition phase, immediately after it, or before the retrieval phase to determine the stage of information processing affected by treatments. Doses of galanthaminium bromide and RS 67333, without effect on their own, jointly improved both place and object recognition in young adult rats via an enhancement of acquisition and consolidation information processing. In old rats, the combined treatment enhanced performance by acting on the acquisition processes of place recognition and on the acquisition and consolidation processes of object recognition. These results indicate that combining agents that act on different neuronal targets may be more powerful than either treatment alone, enabling use of lower doses of each compound, thereby attenuating the adverse effects of the individual drugs. A bitherapeutic strategy of this kind might thus be of interest in the treatment of the cognitive deficits related to "normal" or pathological aging.
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PMID:Combined treatment with galanthaminium bromide, a new cholinesterase inhibitor, and RS 67333, a partial agonist of 5-HT4 receptors, enhances place and object recognition in young adult and old rats. 1255 43

This study was meant to analyze the neural control of the branchial muscles of the clam Mercenaria mercenaria. Gills isolated from the animal contract in response to 5-hydroxytryptamine (5HT), dopamine (DA), and acetylcholine (ACh); but the ACh contraction occurred only if the gills had been pretreated with the cholinesterase inhibitor eserine. The 5HT antagonists cyproheptadine and mianserin blocked the contractile effects of all of the agonists. However, gills exposed to the 5HT antagonists and eserine relaxed in response to ACh. The DA antagonist SCH-83566 inhibited the effects of DA, but had no effect on contractions induced by 5HT and ACh. The ACh antagonist hexamethonium inhibited both the excitatory and inhibitory effects of ACh, but had no effect on contractions induced by 5HT and DA. 5HT and DA in gill tissue were visualized by using immunohistochemistry. Within each gill filament are dorsoventral neurons running adjacent to the epithelium and containing immunoreactive 5HT and DA. A complex network of 5HT-positive fibers is associated with the septa, blood vessels, and muscles, whereas DA-positive fibers are restricted to the septa. We propose that 5HT is the excitatory transmitter to the gill muscles, and that DA and ACh exert their excitatory effects by stimulating 5HT motor nerves. ACh may also be an inhibitory transmitter of the muscles.
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PMID:Branchial musculature of a venerid clam: pharmacology, distribution, and innervation. 1258 47


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