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)

We aimed to determine whether the cholinesterase inhibitor rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), would improve quality of life and cognitive function in 16 clinically stable subjects affected by schizophrenia in the residual phase. Study subjects began rivastigmine treatment at a dose of 1.5 mg bid. This dose was escalated at monthly intervals in increments of 1.5 mg bid to a maximum of 6 mg bid. All subjects were followed for 12 months. Quality of life was assessed using the Satisfaction with Life Domains Scale (SLDS, a self-report scale containing 10 "satisfaction" items); cognitive function, attentional function, and aspects of learning and memory were evaluated using common neuropsychological tests. Psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS). Rivastigmine treatment resulted in significant improvements in quality of life, which were paralleled by significant improvements in cognitive function, learning and memory, and trends for improvement in attention. The BPRS factor "anergia" showed significant improvement, while low baseline scores in other psychotic factors did not permit further improvements. There were no reports of nausea or vomiting. In conclusion, rivastigmine significantly improved quality of life in subjects with schizophrenia. These benefits may relate to the drug's effects on cognitive deficits and negative symptoms associated with the condition.
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PMID:Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. 1464 12

Neurologists and ophthalmologists should be familiar with the causes and treatment of visual hallucinations so that they are able to reassure patients and minimize the anguish associated with untreated visual hallucinations. Hallucinations are under-reported by patients because of the perceived psychiatric implication or because of poor insight into the unreal nature of the hallucinations. In the appropriate setting, physicians should specifically inquire about hallucinations as well as initiate medical treatment. Visual hallucinations have many etiologies and are associated with a variety of disorders. Identification of the associated disorder or cause is necessary to determine the appropriate treatment. Causes and associated disorders include ocular phenomena, migraine, seizures, visual loss (ie, release hallucinations), neurodegenerative disorders, midbrain injury, alcohol and drug effects, narcolepsy, post-traumatic stress disorder, and psychosis. Therapeutic treatment should be directed at the associated disorder or etiology. For instance, antiepileptic drugs may be appropriate for patients with irritative phenomena such as seizures and visual aura of migraine. Depending on the cause, other agents are available and include neuroleptics, cholinesterase inhibitors, and acetazolamide. Well-designed, randomized, controlled clinical trials regarding treatment of visual hallucinations associated with various disorders are lacking. Although complete resolution of visual hallucinations can be difficult, even minimal improvement may be symptomatically beneficial.
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PMID:Visual Hallucinations. 1466 72

Historically, drugs that increase central cholinergic transmission have primarily been investigated for relieving cognitive symptoms in mild-to-moderate Alzheimer's disease. These efforts have led to the somewhat unexpected findings that cholinergic therapy has a beneficial effect on selected neuropsychiatric symptoms in AD across disease stages. In Parkinson's disease with dementia and dementia with Lewy bodies, cholinergic deficits are more severe than in AD, and there is emerging evidence that cholinesterase inhibitors are efficacious in treating core symptoms of attentional disturbance and psychosis. Recent data also suggest a rational basis for cholinergic therapy in vascular dementia. The cognitive and neuropsychiatric effects of cholinergic therapy observed in AD and other dementias form the crux of an integrative model of cholinergic therapeutic efficacy that encompasses the diverse central nervous system actions of acetylcholine and its complementary interactions with central monoamine transmitters. This heuristic framework highlights the broader therapeutic potential of cholinergic therapy for symptom-based indications in other neuropsychiatric disorders.
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PMID:Cholinesterase-inhibitor therapy for dementia: novel clinical substrates and mechanisms for treatment response. 1503 99

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

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

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

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.
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PMID:Treatment of behavioural symptoms and dementia in Parkinson's disease. 1581 Aug 93


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