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

We present the case of a patient with Huntington's disease and psychosis, whose motor and psychiatric symptoms improved after administration of galantamine, an acetylcholinesterase inhibitor.
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PMID:Treatment of Huntington's disease with galantamine. 1510 72

Parkinson's disease (PD) is a chronic neurodegenerative disease, in which mainly dopaminergic neurons in the substantia nigra in the brain degenerate, leading to a depletion of dopamine (DA) in the striatum. The most important motor disturbances of the disease are bradykinesia (slowing down of movement), hypokinesia (poverty of movement), rigidity (muscle stiffness), tremor and postural instability. Besides these well-known motor symptoms, non-motor symptoms may develop, such as depression, cognitive impairment and psychosis. Psychotic symptoms constitute a relatively common but nevertheless serious complication, with visual hallucinations and paranoid delusions often being most prominent. These symptoms are important contributors to patient and caregiver distress and are often important risk factors for nursing home placement. Exogenous (related to therapeutic interventions) factors are of major importance but endogenous (related to the disease process itself) factors might also contribute to the development of psychotic symptoms in PD. Therapeutic strategies comprise reduction of antiparkinsonian treatment, cholinesterase inhibitors and atypical antipsychotics. As psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of strategies may be chosen.
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PMID:Psychotic symptoms in Parkinson's disease: pathophysiology and management. 1515 49

Recent data indicate that patients with vascular dementia (VaD) show a cholinergic deficit. Having obtained good results in a previous study comparing rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholine-sterase (BuChE), vs. aspirin, we aimed to compare the efficacy and tolerability of rivastigmine vs. aspirin plus nimodipine. Patients with a diagnosis of dementia and probable VaD received rivastigmine 3-6 mg/day (n = 32) or aspirin plus nimodipine (n = 32) in an open study for 16 months. Patients treated with rivastigmine showed superior benefits, compared with those receiving aspirin plus nimodipine, in attention, executive function, instrumental activities of daily living, and behavioural and psychotic disturbances. Side-effects in both groups were tolerable and there were no study withdrawals. The benefits observed with rivastigmine may reflect its inhibitory effects on AChE and BuChE, and the drug's affinity for frontal brain areas.
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PMID:Rivastigmine superior to aspirin plus nimodipine in subcortical vascular dementia: an open, 16-month, comparative study. 1516 Nov 18

Increasing evidence suggests that the cholinergic system is involved in the pathogenesis of schizophrenia. Donepezil, a central cholinesterase inhibitor, improves psychotic symptomatology in demented patients, however, evidence for its role in the management of active psychosis in schizophrenia remains limited. An 18-week double blind cross-over study was conducted in which eight patients were randomly assigned to either donepezil (5 mg/day for the first 4 weeks and 10 mg/day for the following 4 weeks) or placebo as augmentation treatment to clozapine. After this initial phase, there was a 2-week washout period of the study medication after which the same regimen was crossed over at the same dose and for the same period (8 weeks). No significant difference was noted in the total positive and negative symptom scale scores when donepezil was compared with placebo (16.7%+12.97% vs 3.20%+13.94% respectively, p = 0.18). However, three patients improved (>15%) in the total PANSS scores (37.03%, 16.6% and 25.33%) during the donepezil treatment phase, while only one patient improved (20.87%) during the placebo phase. No differences were noted in the Calgary depression scale (p = 0.305), Simpson Angus scale (p = 0.374), clinical global impression-improvement scale (p = 0.23) and clinical global impression-severity of illness scores (p = 0.116). Although this preliminary study failed to demonstrate a clear effect of donepezil augmentation in clozapine treated chronic schizophrenia patients, it seems that the subtle positive effect of donepezil observed in some of our patients should encourage further investigation in a larger sample of this patient subpopulation.
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PMID:Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a double blind cross-over study. 1525 26

Memantine is an NMDA receptor antagonist with moderate affinity, which results in neuroprotective potential due to reducing overstimulation caused by glutamate (excitotoxicity) and simultaneous lack of adverse events (especially psychosis) typical for an antagonist with higher affinity like phencyclidine. In randomized, controlled studies it has been shown that memantine is beneficial in the treatment of moderate to severe dementia of Alzheimer's type and it became the very first compound to be registered for this purpose both in Europe (including Poland) and in the United States. Further investigation require usefulness of memantine in less advanced stages of Alzheimer's disease as well as other types of dementia especially vascular; promising results are shown in dual therapy: memantine + cholinesterase inhibitor.
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PMID:[The clinical relevance of memantine use]. 1530 96

Psychosis in Parkinson's disease (PD) is a fairly common and vexing problem. Although it can occur at any stage of the illness, it is a particularly important issue for patients who are in the later stages of PD and have been chronically treated with anti-PD medications. The exact pathophysiology of PD-related psychosis remains a mystery. Neurochemical imbalances, sleep disturbances, and visual processing abnormalities in PD have been implicated in its pathogenesis. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's anti-PD medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic agent is presently the treatment of choice. An emerging treatment option is the use of acetylcholinesterase inhibitors. This article reviews what is known about the epidemiology, risk factors, pathophysiology, and treatment of PD-related psychosis.
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PMID:Psychosis in Parkinson's disease. 1531 76

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Patients also frequently have noncognitive symptoms, such as anxiety, depression, apathy, and psychosis, that impair daily living. The most commonly prescribed treatments for Alzheimer's disease are acetylcholinesterase inhibitors, such as donepezil and galantamine. Enhanced cholinergic functions caused by these compounds are believed to underlie improvements in learning, memory, and attention. The noncognitive aspects of dementia, however, are usually linked to serotonin and dopamine rather than acetylcholine because those neurotransmitter systems most directly influence mood, emotional balance, and psychosis. Fast-scan cyclic voltammetry applied to mouse striatal brain slices was used to measure the real-time release of dopamine arising from spontaneous activity or from single electrical stimulations. At concentrations that include their prescribed dosage ranges, donepezil (1-1000 nM) and galantamine (50-1000 nM) increase action potential-dependent dopamine release. Consistent with previous literature, the data support slightly different modes of action for donepezil and galantamine. The ability of these commonly prescribed drugs to alter catecholamine release may underlie their influence over noncognitive symptoms of dementia. Furthermore, these results suggest that acting via nicotinic receptors, these drugs may serve presently untapped therapeutic roles by altering dopamine release in other disorders involving dopaminergic systems.
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PMID:Cholinergic drugs for Alzheimer's disease enhance in vitro dopamine release. 1532 45

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder mainly characterized by degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area, in combination with a varying loss of central noradrenergic (locus coeruleus), cholinergic (nucleus basalis of Meynert) and serotonergic (dorsal raphe nuclei) integrity, leading to a multitude of motor and non-motor behavioral disturbances. Apart from the clinical motor hallmarks, in the early stages of disease, subtle cognitive dysfunction might be seen comprising mainly executive dysfunction, with secondary visuospatial and mnemonic disturbances. In about 20-40% of patients, these problems may eventually proceed to dementia, which constitutes an important risk factor for caregiver distress, decreased quality of life and nursing home placement. Dementia in PD is typically characterized by a progressive dysexecutive syndrome with attentional deficits and fluctuating cognition, often accompanied by psychotic symptoms. It is thought to be the result of a combination of both subcortical and cortical changes. PD-related dopaminergic deficiency in the nucleus caudatus and mesocortical areas (due to degeneration of projections from the substantia nigra and ventral tegmental area) and cholinergic deficiency in the cortex (due to degeneration of ascending projections from the nucleus basalis of Meynert), combined with additional Alzheimer-pathology and cortical Lewy bodies, may greatly contribute to dementia. Current treatment of dementia in PD is based on compensation of the profound cholinergic deficiency. Recent studies with the cholinesterase inhibitors galantamine, donepezil and rivastigmine show promising results in improving cognition and ameliorating psychotic symptoms, which must further be confirmed in randomized controlled trials.
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PMID:Cognitive dysfunction and dementia in Parkinson's disease. 1548 Aug 40

Delirium is commonly encountered in elderly patients in general hospitals. Most patients with delirium respond well within 12 days of commencement of treatment with haloperidol. A significant number of patients, however, does not improve. Three elderly male patients aged 85, 79 and 81 respectively suffering from prolonged delirium and unresponsive to haloperidol or atypical anti-psychotic drugs, responded well within days to treatment with rivastigmine--a cholinesterase-inhibitor. It was very well tolerated. In The Netherlands cholinesterase inhibitors are registered for the symptomatic treatment of Alzheimer's disease. There is some evidence, both from animal and human experiments, that cholinergic deficiency plays a role in certain types of delirium. Therefore treatment of delirium with a cholinesterase-inhibitor seems logical. Controlled studies are needed to evaluate the effects of these types of drugs in patients with prolonged delirium.
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PMID:[Successful treatment of three elderly patients suffering from prolonged delirium using the cholinesterase inhibitor rivastigmine]. 1555 63

Cognitive impairment in schizophrenia occurs in the early phases of the disease and remains throughout its course. The basis for cognition lies in two main brain regions: the prefrontal cortex and hippocampus. Positron emission tomography, functional magnetic resonance imaging, and proton magnetic spectroscopy studies have shown that prefrontal cortex and hippocampus activity and cell density are lower in patients with schizophrenia than in healthy controls. Dopamine remains the fundamental neurotransmitter involved with schizophrenia. Catechol- O -methyltransferase accounts for about 60% of dopamine metabolism in the prefrontal cortex. Functional polymorphism for the catechol- O -methyltransferase genotypes has been identified in patients with schizophrenia. Those with the valine-valine genotype demonstrate rapid inactivation of dopamine, and performance in cognitive testing in patients is poorer with this allele than with other genotypes. N -methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate acid receptors are also strongly associated with cognitive impairment. Changes occur in apolipoproteins D and E, cholinesterase enzyme activity, neurotensin, and neural growth factors, leading to a possible neurodegenerative process and cognitive impairment in patients with schizophrenia. A fundamental link between psychosis and neurocognition probably arises from complex interactions between these systems at the intracellular secondary messenger system and with protein phosphorylation. Atypical antipsychotics evaluated in receptor models, cell cultures, and animal behavior paradigms indicate that these agents may provide neuroprotective effects. Clinical studies with atypical antipsychotics have consistently demonstrated improvement in cognitive symptoms, and such improvement appears to be correlated with improvement of negative symptoms. A neurodevelopmental model of cognitive impairment in schizophrenia aids in understanding why atypical antipsychotics improve cognitive symptoms.
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PMID:Implications for atypical antipsychotics in the treatment of schizophrenia: neurocognition effects and a neuroprotective hypothesis. 1558 43


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