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)

Twenty-three inpatients who met DSM-III criteria for schizophrenia were selected for cerebrospinal fluid (CSF) neurochemical study of tardive dyskinesia (TD). Ten inpatients had tardive dyskinesia, and the remaining 13 patients without TD served as controls. There were no intergroup differences in sex, age, duration of neuroleptic treatment, or in total amount of neuroleptics received between the TD and the control groups. Cerebrospinal fluid was collected by lumbar puncture, and concentrations of homovanillic acid (HVA), MHPG, 5-hydroxyindoleacetic acid (5-HIAA), and acetylcholinesterase (AChE) activity were measured. The concentrations of MHPG (TD 11.56 +/- 3.48 ng/ml versus control 14.20 +/- 3.86 ng/ml), 5-HIAA (45.27 +/- 9.77 ng/ml versus 40.34 +/- 13.77 ng/ml), and HVA (38.26 +/- 18.31 ng/ml versus 31.40 +/- 7.83 ng/ml), and the activity of AChE (TD 7.95 +/- 5.21 mmol/g.hr versus control 12.89 +/- 8.04 mmol/g.hr) showed no significant differences between the two groups, but the ratios of HVA/AChE (t = 2.21, p = 0.05), 5-HIAA/AChE (t = 2.62, p = 0.02), MHPG/HVA (t = -2.16, p = 0.04), and MHPG/5-HIAA (t = -2.48, p = 0.02) were statistically different. The results indicated that TD might involve an imbalance of dopamine-acetylcholine, noradrenalin-dopamine, noradrenalin-serotonin, and serotonin-acetylcholine.
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PMID:CSF neurochemical study of tardive dyskinesia. 246 90

A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood groups revealed that none other than peptidase A showed significant linkage with affective disorder since one significant finding is expected by chance. We conclude from the overall morbid risk data and segregation analyses that bipolar manic-depressive illness is a spectrum disease inherited through a multifactorial mode of genetic transmission (which is not synonymous with polygenetic inheritance) with possible genetic heterogeneity and find no evidence for X-linkage. Additional studies with acetylcholinesterase, haptoglobin, GC, and properdin-factor B are needed to confirm their positive biological/genetic marker value suggested by our long-term epidemiological study.
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PMID:Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders. 651 12

Up to one-third of patients with mild to moderate Alzheimer's disease may show improvement in cognitive function with tacrine, a centrally-acting, noncompetitive inhibitor of acetylcholinesterase. Candidates for tacrine must have a diagnosis of probable Alzheimer's dementia based on NINCDS-ADRDA or DSM-IV criteria and should have no history of liver disease. For patients receiving the drug, do follow-up cognitive testing with a sensitive measure such as the Alzheimer's Disease Assessment Scale. The most common adverse effects associated with tacrine therapy are elevated liver transaminases and gastrointestinal effects. Weekly blood tests are necessary to monitor liver function. A reliable caregiver is essential to ensure compliance with frequent dosing and weekly blood testing.
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PMID:Alzheimer's disease: how to give and monitor tacrine therapy. 760 62

The growth hormone response to the acetylcholinesterase inhibitor pyridostigmine was measured in nine normothymic outpatients who met DSM-III-R criteria for obsessive-compulsive disorder. The responses were significantly elevated when compared to those found in a healthy comparison group (N = 9). The data suggest that cholinergic supersensitivity is present in obsessive-compulsive disorder.
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PMID:Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity. 849 78

This study evaluated the safety and efficacy of idebenone vs. tacrine in a prospective, randomized, double-blind, parallel-group multicenter study in patients suffering from dementia of the Alzheimer type (DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R (primary degenerative dementia) and NINCDS-ADRDA criteria (probable Alzheimer's disease). A total of 203 patients of both sexes aged between 40 and 90 years were randomized to either idebenone 360 mg/day (n = 104) or tacrine up to 160 mg/day (n = 99) and treated for 60 weeks. The primary outcome measure was the Efficacy Index Score (EIS). The EIS combines dropout as well as the relevant improvements individually across the three levels of assessment (cognitive function, activities of daily living, global function). Secondary outcome measures were the ADAS-Cog score, the NOSGER-IADL score and the clinical global response (CGI-Improvement). After 60 weeks of treatment, 28.8 % of the patients randomized to idebenone, but only 9.1 % of the patients randomized to tacrine were still on the drug. In the LOCF analysis, 50 % of the patients randomized to idebenone but only 39.4 % of the patients randomized to tacrine showed an improvement in the Efficacy Index Score or at least one of the secondary outcome variables. The primary efficacy measurement was the change of the Efficacy Index Score from baseline to the assessment after 60 weeks treatment. The analysis was done on intention-to-treat (ITT) in a before-and-after test design. Patients randomized to idebenone showed a higher benefit from treatment than patients randomized to tacrine. We conclude that the benefit-risk ratio is favorable for idebenone compared to tacrine, and furthermore, that this ratio is likely to be similar when comparing idebenone to other cholinesterase inhibitors.
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PMID:Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study. 1181 53

Cholinergic deficits are clinicopathological hallmarks of Alzheimer's disease (DAT) and during the past decade have been the sole target for clinically effective treatments. By contrast, vascular dementia subtypes (VaD) are heterogeneous clinical syndromes, and therapeutic approaches have been directed toward control of vascular risk factors. Little attention has been paid to cholinergic deficits as a mechanism contributing to cognitive impairments in VaD as a potential target for treatment. The purpose of the study was to determine whether there are therapeutic benefits from long-term treatment with cholinesterase inhibitors among VaD patients. Ten VaD patients were diagnosed according to DSM-III-R and NINDS-AIREN criteria and classified into subtypes by neuroimaging. All were treated with titrated doses of donepezil for a mean interval of 15 months. At baseline and follow-up clinic visits, patients underwent medical and neurological examinations, as well as neuropsychological testing including Mini-Mental Status Examinations (MMSE) and Cognitive Capacity Screening Examinations (CCSE). Cognitive statuses of 10 treated patients were then compared before and after treatment. Net changes were expressed as annual MMSE score changes (DeltaMMSE/year) and annual CCSE score changes (DeltaCCSE/year). Of the 10 treated VaD patients, cognitive improvements were found when comparisons were made before and after treatment. Ten treated patients also showed greater cognitive improvements, while untreated patients showed continued cognitive decline. This study suggests that cholinergic deficits in VaD are due to neuronal ischemic damage with loss of acetylcholine and that treatment of VaD with cholinesterase inhibitors is a rational therapy.
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PMID:Donepezil treatment of vascular dementia. 1248 Jul 89

Although there have been several case reports suggesting the beneficial effect of acetylcholinesterase inhibitors in the cognitive deficits seen in schizophrenia, controlled studies have revealed contradictory results. The aim of this study was to investigate if donepezil could improve cognitive functions in schizophrenia. Twelve schizophrenic patients, who were diagnosed according to DSM-IV criteria and who had been on a stable dose of a high-potency typical antipsychotic for a minimum period of 3 months, participated in this 12-wk double-blind, placebo controlled, cross-over study of donepezil adjunctive treatment. Patients were randomly assigned under double-blind conditions to receive 5 mg/d donepezil or placebo for 6 wk, and then were crossed over to the alternate condition for 6 additional weeks. At baseline, 6 and 12 wk, patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, the Wechsler Memory Scale Revised (WMS-R), a test for Verbal Fluency, Trail Making Test, Parts A and B, and Wisconsin Card Sorting Test (WCST). Treatment effect was not significant in any of the cognitive measures. There were also no significant changes in the PANSS and depression scores. Nicotinic receptor desensitization may cause non-responsiveness to acetylcholine as previously suggested, but the most likely explanation appears to be that defects in other neurotransmitter systems account for the cognitive deficits seen in schizophrenic patients.
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PMID:A double-blind, placebo controlled, cross-over trial of adjunctive donepezil for cognitive impairment in schizophrenia. 1474 Oct 60

Approximately 25% of patients with idiopathic Parkinson's disease (IPD) later develop dementia, with the typical characteristics as detailed in ICD-10 and DSM-IV. Differential diagnosis has to exclude dementia due to Lewy bodies, subcortical vascular encephalopathy and subcortical dementia due to progressive supranuclear paralysis or corticobasal degeneration. Several studies showed promising results for cholinesterase inhibitors such as donepezile, rivastigmine and galantamine. The demented Parkinsonian patients then present with improvement in cognitive function while motor skills do not deteriorate.
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PMID:Dementia in idiopathic Parkinson's syndrome. 1567 22

Alzheimer's disease (AD) is characterized by an extensive loss of cholinergic neurons, and their cortical projections, from the basal forebrain area. The resulting reduction in cholinergic activity is associated with decreased levels of the neurotransmitter acetylcholine (ACh), decreased activity of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased butyrylcholinesterase (BChE) activity. In the present study, we investigated whether the BCHE, ACHE, and CHAT genes were associated with AD and the possibility of a synergistic effect with APOE-epsilon4 in a Sardinian sample. AD patients (n = 158), exclusively of Sardinian ancestry, were recruited from the Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology, Department of Neurosciences, University of Cagliari. Patients were diagnosed according to DSM-IV, and National Institute of Neurologic and Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) criteria for possible or probable AD. Cognitive screening was performed by means of Mini-Mental State Examination (MMSE). Healthy controls (n = 118) of Sardinian ancestry were recruited from religious and sport associations. All patients and control subjects gave informed consent for participation in the study. Single nucleotide polymorphism (SNP) analysis was performed by PCR/RFLP or the TaqMan 5' exonuclease method. Our study confirms the association between APOE epsilon4 allele and AD (P < 0.000). No significant differences were observed in allele and genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype analysis of ACHE SNPs did not reveal a significant association between ACHE and AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not constitute a major genetic risk factor for susceptibility to AD in a Sardinian population.
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PMID:Alzheimer's disease: case-control association study of polymorphisms in ACHE, CHAT, and BCHE genes in a Sardinian sample. 1750 75

There is considerable incentive to develop new treatment strategies that effectively target cognitive deficits in schizophrenia. One of the theoretically promising novel treatment candidates is acetylcholinesterase inhibitors that increase the synaptic levels of cholinergic, nicotinic, and muscarinic receptor activity. The purpose of this study was to assess the efficacy of donepezil as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. This investigation was a 12-week, double-blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments, age ranging from 22 to 44 years. All participants met DSM-IV-TR. diagnostic criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive donepezil (10 mg/day) or placebo, in addition to risperidone (4-6 mg/day). Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed by a psychiatrist at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The donepezil group had significantly greater improvement in the negative symptoms over the 12-week trial. There were no differences between the donepezil and placebo groups on any neurocognitive assessments at endpoint (week 12). The present study indicates donepezil as a potential adjunctive treatment strategy for negative symptoms of chronic schizophrenia.
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PMID:A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia. 1872 48


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