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 distribution of the plasma cholinesterase variants found in 1,374 mentally ill patients differs from that of a random control sample. The patients are more likely to have a rare phenotype than an individual from the normal population. None of the diagnostic groups have been shown to differ in the distribution of the E1a gene, but there is strong statistical evidence that Group IV (psychosis) patients have a higher frequency of the E1f gene than the other groups. The overall frequency of the electrophoretic variant C5 + did not differ significantly from that observed in a Caucasian population, with the exception of the increase observed in Group IV c2. Twenty-eight unrelated patients with Huntington's chorea were found to have a significantly altered incidence of the C5 + variant and six patients from this group were found to have the rare E1f gene. Our results indicate that the plasma cholinesterase variants may provide some insight into the inheritance of Huntington's chorea.
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PMID:The plasma cholinesterase variants in mentally ill patients. 13 58

Cerebrospinal fluid (CSF) acetylcholinesterase (AChE) was determined for 11 chronic schizophrenic patients with dementia, 9 patients with dementia associated with alcoholism and 8 age-equivalent control subjects. The AChE levels in both patient groups were unrelated to the degree of cognitive decline and they were in the same range as in the control group. In schizophrenic patients no relationship was found between CSF AChE and the severity of psychotic symptoms. Our results suggest that dementia may occur in these patient groups without CSF AChE involvement.
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PMID:Cerebrospinal fluid acetylcholinesterase in patients with dementia associated with schizophrenia or chronic alcoholism. 188 96

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49

The clinical manifestations of so-called 'untreatable dementias' result from neuronal dysfunction causing premature neuronal death. As long as the neurosciences won't have an explanation for the increased vulnerability and cause of death of neurons in neurodegenerative disorders, no preventive or curative treatment can be expected. So far, the treatment of dementia focuses essentially on the consequences of neuronal dysfunction or cell loss by either a palliative approach addressing psychosis, behavior or anxiety and depression, or by substitution of deficient neurotransmitters with quasi no success. Only tacrine, a cholinesterase inhibitor, now available in Switzerland, has a marginal effect in early cases, but every other substitutive approach has failed so far. Muscarinic agonists as well as antiamyloid substances will be tested soon in clinical trials. Growth factors (especially NGF) raise big hopes for the near future, but they are still under preclinical evaluation.
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PMID:[Toward a treatment for dementia]. 748 4

Patients who present with acute neuropsychiatric syndromes pose difficult diagnostic and treatment challenges. A history of psychiatric illness and treatment with psychotropic medication may be valuable clues to diagnosis and management of such patients. However, this information may also tempt a clinician to focus on a premature diagnosis, excluding other important possibilities. A case of a 42-year-old male with recurrent psychotic illness who developed an abrupt deterioration in mental and physical status is presented. Despite an initial good response to physostigmine, he was diagnosed with neuroleptic malignant syndrome and did not receive subsequent treatment with cholinesterase inhibitors. The patient expired within hours of arriving in the emergency room. The postmortem benztropine level was elevated, leading to the attribution of death to anticholinergic toxicity. This case serves to illustrate the difficulties in distinguishing features of anticholinergic toxicity and neuroleptic malignant syndrome.
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PMID:Anticholinergic toxicity masquerading as neuroleptic malignant syndrome: a case report and review. 764 37

Deficits in early stages of information processing, specifically the inability to "disattend" irrelevant stimuli and to selectively allocate processing resources (i.e., hyperattention), have been associated with the development of psychotic symptoms. Opposite deficits, i.e., the failure to attend and select stimuli, and to divide attention (i.e., hypoattention), represent a major variable in the development of dementia. The hypothesis that hyperattention and hypoattention are mediated via cortical cholinergic hyperactivity and hypoactivity, respectively, is discussed. Several lines of evidence support the role of cholinergic hyperactivity in the development of psychotic symptoms, including the therapeutic effects of anticholinergic drugs in schizophrenic patients, the psychotic effects of chronic exposure to irreversible cholinesterase inhibitors, and the worsening of psychotic symptoms as a result of the treatment with cholinomimetic compounds. The potent impairments of attentional abilities as a result of the administration of muscarinic antagonists in intact subjects, and the attentional effects of cholinomimetic compounds in demented patients are two examples of the evidence that supports the role of cholinergic hypofunction in the cognitive impairments of dementia. A neuronal model of dopamine-GABAergic modulation of cortical acetylcholine is proposed on the basis of evidence indicating that nucleus accumbens dopamine, via a GABAergic pathway to the substantia innominata of the basal forebrain, modulates cortical acetylcholine release. The available evidence confirms several predictions derived from this model, including the dopaminergic regulation of cortical acetylcholine (ACh) release, the bidirectional modulation of this release by benzodiazepine receptor (BZR) agonists and inverse agonists, and the antipsychotic effects of BZR agonists. Bidirectional deviations in the activity of cortical cholinergic inputs are hypothesized to represent a major neuronal substrate of the attentional dysfunctions associated with, or even underlying, the development of psychotic symptoms and dementia.
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PMID:Neuronal mechanisms of the attentional dysfunctions in senile dementia and schizophrenia: two sides of the same coin? 785 15

A 53-year-old Japanese woman with a point mutation in mitochondrial DNA (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type brain pathology is reported. This woman had suffered myopathy and psychosis without any clinical evidence of, stroke-like episodes during the last 10 years of her life, and had died after an accident. At autopsy 30 h post mortem, a part of the brain was snap frozen for biochemical and histochemical studies, and the remaining part was processed for a routine examination and electron microscopy. In the brain there were no ischemic lesions. Instead, primitive/diffuse senile plaques were found throughout the brain, predominantly in the frontal and temporal lobes, while Alzheimer neurofibrillary tangles were found only in the parahippocampal gyrus. These plaques were positive for beta-protein and mostly negative for tau protein, ubiquitin, neurofilaments, alpha-choline acetyltransferase, and acetylcholinesterase. Mutations in codon 331 of the ND2 gene as well as codons 693, 713 and 717 of the beta-amyloid precursor protein gene, known to be responsible for some cases of familial Alzheimer disease, were not found. Furthermore, coincidental Down syndrome was ruled out by chromosome analysis. The results suggest a possible correlation between this mitochondrial DNA abnormality and Alzheimer-type pathology.
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PMID:Alzheimer-type pathology in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). 887 Aug 35

Agitation or psychosis or both occur in half or more of patients with dementia at some point during the course of illness. The treatment of these signs and symptoms ideally entails identification and alteration of physical, environmental, social, and psychiatric factors. Environmental modification, education of caregivers, and therapeutic activity programs are nonpharmacologic approaches that can effectively reduce some signs and symptoms of this nature. For those that remain, empirical administration of pharmacologic agents may be appropriate. One approach is to inventory the specific behaviors and develop a "therapeutic metaphor," i.e., subtype the agitated behaviors according to the presence of target symptoms likely to respond to specific classes of medication. Available evidence is reviewed regarding the efficacy and safety of somatic therapies for agitation, including antipsychotics, antidepressants, anticonvulsants, benzodiazepines, and cholinesterase inhibitors.
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PMID:Treatment strategies for agitation and psychosis in dementia. 902 33

Disruptive agitation and psychotic symptoms are important problems in the management of Alzheimer's disease and are major determinants of nursing home placement. This article reviews interpretable, placebo-controlled studies of psychopharmacologic approaches to the treatment of these "noncognitive" psychiatric and behavioral problems. Clinical trials of antipsychotic drugs demonstrate modest efficacy for psychosis and agitation, but adverse effects are common. Trials of serotonin selective reuptake inhibitors suggest they may be effective for emotional disturbances complicating Alzheimer's disease. Trials of drugs that enhance central cholinergic activity (certain cholinesterase inhibitors and selective M1 muscarinic cholinergic agonists) demonstrate positive effects on both cognitive deficits and noncognitive psychiatric and behavioral problems. Further clinical studies are needed to provide guidelines for the management of noncognitive psychiatric and behavioral problems in Alzheimer's disease.
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PMID:Psychopharmacology of noncognitive abnormal behaviors in Alzheimer's disease. 972 Apr 84

Delirium is a common complication of dementia and may produce considerable morbidity. In addition to psychotic symptoms such as hallucinations and delusions, delirium may produce considerable agitation, which may be refractory to conventional medications such as antipsychotics and benzodiazepines. The main approach to delirium is to treat any underlying medical problem that could cause the delirium. However, delirium is not always reversible, and there is no specific treatment for persistent delirium. The authors present a case of delirium complicating a preexisting dementia that resolved rapidly following initiation of the cholinesterase inhibitor donepezil, suggesting that cholinergic dysfunction may have played a role in the etiology of this patient's delirium. Future research needs to be directed at the issue of cholinergic activity in delirium through monitoring of serum anticholinergic activity and its response to procholinergic therapy.
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PMID:Donepezil improves symptoms of delirium in dementia: implications for future research. 989 35


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