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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the low basal output, measurement of acetylcholine (ACh) release from enteric neurons usually requires cholinesterase inhibition, a condition which is known to interfere with feed-back mechanisms regulating ACh release. In this study, we resorted to a highly sensitive HPLC-ED method to determine the minimum requirement of physostigmine to achieve reliable quantitation of spontaneous endogenous ACh overflow from the guinea-pig isolated colon. Furthermore, in order to assess the degree of interference by physostigmine with cholinergic function, we assessed the effect of scopolamine and oxotremorine (in the presence of physostigmine) on spontaneous ACH overflow (to detect the presence of autoreceptors) and also measured the efficiency of the peristaltic reflex with different physostigmine concentrations. Spontaneous endogenous ACh overflow was detectable only with physostigmine concentrations > or = 10 nM. ACh overflow increased with increasing physostigmine concentrations (10 nM-10 microM range). Scopolamine significantly enhanced the facilitatory effect of physostigmine concentrations > or = 10 nM; conversely, oxotremorine inhibited ACh overflow. Peristaltic efficiency was not significantly affected by physostigmine concentrations < or = 300 nM. In conclusion, this modified HPLC-ED method allows ACh detection with minimal physostigmine concentrations (10-30 nM), which do not interfere with peristaltic activity, do not saturate autoreceptor feed-back mechanisms and therefore improve the assessment of cholinergic function in colonic enteric neurons.
...
PMID:Acetylcholine detection by a modified HPLC-ED method improves the assessment of cholinergic function in the myenteric plexus of the guinea-pig colon. 929 79

The effects of the muscarinic antagonists, scopolamine HBr and MeBr, a cholinesterase inhibitor, E2020, and K+ channel blockers, 4-aminopyridine (4-AP) and apamin, on the performance of rats in a delayed matching to position (DMTP) task were examined. The percentage of correct choices (choice accuracy), number of trials completed and intertrial intervals were measured. Discriminability and response bias were also calculated, using signal detection analysis. Scopolamine HBr (0.1 mg/kg), but not scopolamine MeBr (0.1 mg/kg), significantly and consistently reduced the choice accuracy and discriminability, but neither affected the other measurements. E2020 (0.03-1.0 mg/kg) had no effect on the baseline performance in the DMTP task, but at 1.0 mg/kg, it significantly attenuated the deficits in choice accuracy induced by scopolamine. 4-AP (0.001-0.1 mg/kg) had no effect on either baseline performance or deficits induced by scopolamine. Apamin (0.1-0.4 mg/kg) had no effect on choice accuracy and discriminability. Apamin also failed to attenuate the scopolamine-induced deficits. When administered in combination with scopolamine, apamin at 0.4 mg/kg significantly decreased the number of trials completed and increased the intertrial interval relative to that of the control group. Taken together, these results demonstrate that K+ channel blockers (4-AP and apamin), unlike a cholinesterase inhibitor (E2020), fail to reverse the scopolamine-induced deficits in the DMTP task.
...
PMID:Effects of the potassium channel blockers, apamin and 4-aminopyridine, on scopolamine-induced deficits in the delayed matching to position task in rats: a comparison with the cholinesterase inhibitor E2020. 949 27

The purpose of our studies was to determine the effects of muscarinic receptor agonists on conditioned avoidance responding in the rat. Rats were trained to avoid or escape an electric shock delivered to the feet in a discrete trial procedure. The muscarinic receptor agonists pilocarpine and [2-ethyl-8-methyl-2,8-diazaspiro(4. 5)decane-1,3-dione] hydrochloride (RS86) and the cholinesterase inhibitor physostigmine all decreased the percentage of avoidance responses at doses that produced less than approximately 30% response failures. Similar results were obtained with the antipsychotic drugs haloperidol, trifluoperazine, chlorpromazine, and clozapine. However, the benzodiazepine anxiolytic diazepam did not decrease avoidance responding up to doses that produced ataxia. On the other hand, oxotremorine and arecoline decreased avoidance responding only by producing response failures, whereas aceclidine produced intermediate changes. The muscarinic receptor antagonists scopolamine, trihexyphenidyl, and benztropine were without effect when administered alone but antagonized the decreases in avoidance responding produced by pilocarpine and RS86. Scopolamine had little effect on the decreases in avoidance responding produced by haloperidol. The newer muscarinic receptor partial agonists or agonist/antagonists [R-(Z)-(+)-alpha-(methoxyimino)-1-azabicyclo[2.2. 2]octane-3-acetonitrile] hydrochloride, talsaclidine, milameline, and xanomeline also produced dose-related decreases in avoidance responding. Our results demonstrate that muscarinic receptor agonists can decrease avoidance responding in a manner similar to dopamine-receptor antipsychotic drugs, suggesting that muscarinic receptor agonists may provide an alternative approach to the treatment of psychosis.
...
PMID:Muscarinic receptor agonists, like dopamine receptor antagonist antipsychotics, inhibit conditioned avoidance response in rats. 1041 7

Location precues were used to manipulate the spatial scale of attention in visual search for a target in an array of letters in patients with dementia of the Alzheimer type (DAT) and in age-matched older controls. Cue size varied in the amount of spatial precision conferred. Scopolamine, a muscarinic antagonist, decreased overall arousal and broadened spatial attention after a precise precue (small and valid) to target location for DAT patients but not for controls, suggesting a selective effect for attentional impairment induced by cholinergic blockade. In contrast, physostigmine, a cholinesterase inhibitor, did not alter the distribution of spatial attention relative to no-drug baseline testing for patients. Results support a differential role for cholinergic mechanisms in the modulation of the spatial scale of visual attention.
...
PMID:Acetylcholine affects the spatial scale of attention: evidence from Alzheimer's disease. 1079 68

Donepezil is a member of a new class of centrally acting cholinesterase inhibitors which preferentially inhibit acetylcholinesterase rather than butyrylcholinesterase. The effects of donepezil on learning impairments were investigated in some hypocholinergic models in rats. In nucleus basalis magnocellularis (NBM)-lesioned rats, donepezil alleviated deficits in passive avoidance response at a dose of 0.125 mg/kg and higher, while tacrine had only a tendency toward improved performance. Donepezil at 0.5 mg/kg effectively counteracted acquisition impairments in the water maze task induced by lesions of the medial septum; tacrine had no significant effects on impairments in this task. Scopolamine caused an increase of errors in the 8-arm radial maze. Donepezil significantly decreased scopolamine-induced errors in the radial maze at 0.5 mg/kg, whereas tacrine decreased errors at 2 mg/kg. These results suggest that donepezil can clearly minimize learning impairments induced by treatments that cause central cholinergic deficiencies in rats. These findings support the clinical efficacy of donepezil in Alzheimer's disease.
...
PMID:Donepezil, a centrally acting acetylcholinesterase inhibitor, alleviates learning deficits in hypocholinergic models in rats. 1084 91

This study was designed to investigate the central and peripheral activity profile of cholinesterase inhibitors in rats. Intravenous injection of cholinesterase inhibitors caused fasciculation, a fine involuntary muscular movement. This peripheral cholinergic sign was tightly correlated with in vitro anti-acetylcholinesterase activity by cholinesterase inhibitors, suggesting that fasciculation is a valid index of peripheral cholinergic activation. Yawning, used as a marker of central cholinergic activation, was also monitored. E2030 (3-(2-(1-(1,3-dioxolan-2-ylmethyl)-4-piperidyl)ethyl)-2H-3,4-dihydro-1,3-benzoxazin-2,4-dione hydrochloride) elicited yawning at more than 4 mg/kg, while fasciculation was significantly intensified only at a dose of 16 mg/kg. Donepezil and tacrine induced both yawning and fasciculation at doses greater than 4 mg/kg, whereas physostigmine induced both behaviors at a dose of 8 mg/kg and above. Finally, ipidacrine elicited yawning at a dose of 16 mg/kg and fasciculation at doses greater than 8 mg/kg. Thus, all putative centrally acting cholinesterase inhibitors elicited yawning. TAK-147 (3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-benzazepin-8-yl)-1-propanone fumarate) did not significantly elicit yawning at doses under 16 mg/kg, but elicited fasciculation at a dose of more than 4 mg/kg. Distigmine, a peripherally acting cholinesterase inhibitor, evoked fasciculations, but not yawning. When mild to moderate fasciculation was evoked, donepezil and E2030 elicited more than nine yawns over 30 min, while the other cholinesterase inhibitors elicited approximately five yawns at most during this period. These results indicated that E2030 and donepezil exhibited the most marked preferential central cholinergic activity, relative to peripheral activity, among cholinesterase inhibitors tested. Scopolamine, a centrally acting antimuscarinic drug, completely inhibited E2030-induced yawning, while peripherally acting methylscopolamine did not. Haloperidol, a dopamine receptor antagonist, partially blocked E2030-induced yawning, but did not block donepezil-induced yawning. These results suggest that central cholinergic and, in part, dopaminergic mechanisms are involved in E2030-induced yawning.
...
PMID:Central and peripheral activity of cholinesterase inhibitors as revealed by yawning and fasciculation in rats. 1127 94

Systemically administered cholinomimetics or cholinesterase inhibitors can depress behavior in humans and animals, whereas antimuscarinic agents reverse this effect or even produce euphoria. Although these effects have been well documented, the specific brain regions that mediate them remain largely unknown. In the present experiments, muscarinic agonists and antagonists were locally injected into the nucleus accumbens of female Sprague-Dawley rats to test for their effects on behavioral depression in the Porsolt swim test and locomotor activity. Local, microinjections of the drugs in the accumbens elicited behaviors that were similar to the systemic effects reported in other studies. Injection of the non-specific agonist arecoline (40 and 80 microg) dose-dependently inhibited swimming and escape behavior. This may be mediated in part by accumbens M1 receptors because blocking these receptors with the specific antagonist pirenzepine (17.5 and 35.0 microg) did the opposite by increasing swimming. Gallamine (0.13, 0.44, and 0.88 microg), an antagonist at M2 receptors, dose-dependently decreased swimming. Two-way microdialysis suggested that this was in part due to the release of ACh by blocking M2 autoreceptors. Scopolamine, a mixed M1/M2 receptor antagonist, also released ACh but did not decrease swimming, probably because the M1 receptors were blocked; the drug (1.0 microg) increased swimming time, much like pirenzepine. With the exception of arecoline, none of the drugs significantly affected locomotor activity in a photocell cage. Arecoline (40 microg), which had decreased swimming, reduced activity. The present study suggests that muscarinic receptors in the nucleus accumbens can control immobility in the Porsolt swim test. The onset of immobility may depend on the activation of post-synaptic M1 receptors.
...
PMID:Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test. 1144 Aug 10

The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus (OP) pesticides, fenamiphos and profenofos. Both pesticides produce considerable blood ChE inhibition, but relatively little brain inhibition up to almost lethal doses. Interestingly, pronounced neurobehavioral signs were produced by fenamiphos but not profenofos. After a single oral dose, both pesticides greatly inhibited blood ChE (87-98% inhibition), yet whole brain ChE was only inhibited by 9-14% at the highest doses. Fenamiphos produced dose-dependent effects on many behavioral measures. Despite the similar ChE inhibition profile, profenofos produced no observable changes in behavior. Treatment with anticholinergic drugs was used to evaluate the contribution of peripheral versus central ChE inhibition. Scopolamine (SCO) and methylscopolamine (MSC) were used as central/peripheral and peripheral-only cholinergic receptor blockers, respectively, in combination with fenamiphos. Neither drug altered the effects of fenamiphos on ChE inhibition. Some behavioral effects of fenamiphos were blocked or attenuated only by SCO, whereas other effects were blocked by both drugs. These data indicate that some of the pronounced neurobehavioral changes observed following fenamiphos dosing may be centrally mediated (blocked by SCO only), despite the small amount of inhibition of brain ChE. Other behavioral changes may be mediated more peripherally (blocked by both MSC and SCO). To test the hypothesis that regionally specific ChE inhibition may be responsible for these effects, the same dose of fenamiphos used in the previous studies was given and one half of the brain was dissected into regions. There was significant ChE inhibition in the pons and medulla, cerebellum, striatum, hippocampus, and half-brain but not in the rest-of-brain and frontal cortex; however, the magnitude of inhibition was relatively small across the regions measured. Thus, the centrally mediated neurobehavioral effects of fenamiphos could not be explained based on differential regional brain ChE inhibition alone. Despite the low level of brain ChE inhibition, some behavioral effects of fenamiphos were centrally mediated, and there was little regional specificity of ChE inhibition that could account for the behavioral changes observed.
...
PMID:Differential profiles of cholinesterase inhibition and neurobehavioral effects in rats exposed to fenamiphos or profenofos. 1511 2

The aim of these experiments was to assess whether the clinically validated cognition enhancers donepezil (Aricept, E2020) and metrifonate antagonize scopolamine-induced deficits in the cone field, a complex spatial discrimination task. The cone field task allows measurement of the effects of experimental manipulations on working and reference memory (WM and RM), search strategies, and on the speed and latency to execute the task. The effects of a single administration of donepezil (0.1, 0.3, and 1.0 mg kg(-1), p.o.) and metrifonate (30, 60, and 120 mg kg(-1), p.o.) were investigated in adult Harlan-Wistar rats trained to a stable level of performance and pretreated with scopolamine (0.5 mg kg(-1), i.p. 30 min before training). Scopolamine impaired WM without inducing overt non-cognitive side-effects. Donepezil did not antagonize the scopolamine-induced deficits, whereas metrifonate antagonized the WM deficits at the dose of 60 mg kg(-1), but not at 30 or 120 mg kg(-1). Thus, a cholinesterase inhibitor with proven clinical efficacy can antagonize scopolamine-induced spatial memory deficits. The cone field would be a useful component of a behavioral screening battery to test the effects of putative cognition enhancers.
...
PMID:Effects of the cholinesterase inhibitors donepezil and metrifonate on scopolamine-induced impairments in the spatial cone field orientation task in rats. 1547 45

Cure of cognitive disorders such as amnesia, attention deficit and Alzheimer's disease is still a nightmare in the field of medicine. Nootropic agents such as piracetam, aniracetam and choline esterase inhibitors like Donepezil are being used to improve memory, mood and behavior, but the resulting side effects associated with these agents have made their use limited. The present study was undertaken to assess the potential of Brahmi rasayana (BR) as a memory enhancer. BR (100 and 200 mg kg(-1) p.o.) was administered for eight successive days to both young and aged mice. Elevated plus maze and passive-avoidance paradigm were employed to evaluate learning and memory parameters. Scopolamine (0.4 mg kg(-1) i.p.) was used to induce amnesia in mice. The effect of BR on whole brain AChE activity was also assessed. Piracetam (200 mg kg(-1) i.p.) was used as a standard nootropic agent. BR significantly improved learning and memory in young mice and reversed the amnesia induced by both scopolamine (0.4 mg kg(-1) i.p.) and natural aging. BR significantly decreased whole brain acetyl cholinesterase activity. BR might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly.
...
PMID:Brahmi rasayana improves learning and memory in mice. 1655 Feb 27


<< Previous 1 2 3 4 Next >>

---