Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been proposed that the etiologies of tardive dyskinesia and Huntington's chorea and of some forms of schizophrenia and the affective disorders involve a cholinergic imbalance with respect to a second neurotransmitter. This relative over- or underactivity of the cholinergic system could result from altered synthesis, storage, release, degradation, or reuptake or from a variety of receptor interactions. Under these hypotheses, clinical symptoms would reflect both the brain region in which the imbalance occurs and the neurotransmitter with which acetylcholine is interacting. Effective treatments could involve the correction of this hypothetical imbalance by changing the relative availability of either one or both of the neurotransmitters. Both precursor loading with choline or dimethylaminoethanol and cholinesterase inhibition may be useful in evaluating the effects of increased cholinergic activity in these disease states; the relative merits of these strategies are discussed.
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PMID:Cholinergic imbalance hypotheses of psychoses and movement disorders: strategies for evaluation. 13 84

Perioral behaviors induced by neuroleptic drugs have been interpreted as an animal model of tardive dyskinesia. However, these behaviors have also been induced or enhanced by physostigmine, a cholinesterase inhibitor. The latter result is contradictory to the clinical effect of physostigmine in human tardive dyskinesia. In view of this contradiction and other considerations, perioral behaviors have also been interpreted as a model of acute dystonia. The present experiments replicated an earlier failure to observe spontaneous perioral behaviors after long-term neuroleptic treatment in rats as well as the paradoxical effect of physostigmine. The effect of physostigmine was also compared to phenylmethanesulfonyl fluoride and methanesulfonyl fluoride, irreversible CNS active cholinesterase inhibitors. There were significant differences between the effects of the various cholinesterase inhibitors and their interactions with perioral behaviors and neuroleptic treatment. It is concluded that the effects of cholinesterase inhibitors on perioral behaviors in rodents may not be accounted for entirely by cholinesterase inhibition. Further experiments using additional agonists and antagonists will be required to clarify the behavioral effects of these cholinesterase inhibitors.
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PMID:Perioral behaviors induced by cholinesterase inhibitors: a controversial animal model. 380 24

Delta-9-tetrahydrocannabinol (THC), a substance in marihuana, was found to produce a profound potentiation of reserpine-induced hypokinesia in rats as measured with a bar test. In these experiments, THC had no hypokinetic effect by itself but produced a more than 20-fold increase in the hypokinesia produced by reserpine. Reserpine-induced hypokinesia has been viewed as animal model of Parkinson's Disease. THC potentiation of reserpine-induced hypokinesia was observed to be both time- and dose-dependent (1 to 10 mg/kg THC). When administered by gavage to reserpine-pretreated subjects (7.5 mg/kg IP, 24 hours before), THC produced a potentiation of hypokinesia that developed fully within 1 hour, lasted at least 5 hours, and was absent by 12 hours after THC administration. This THC effect was slightly increased by physostigmine, a cholinesterase inhibitor, relatively unaffected by scopolamine, a muscarinic antagonist, and almost completely blocked by ethopropazine, an anticholinergic antiparkinson drug. The effect was completely unaffected by naloxone. Insofar as reserpine has been used with some clinical efficacy in hyperkinetic movement disorders such as Huntington's disease and tardive dyskinesia, it may be that potentiation of reserpine's hypokinetic effect by a drug such as THC could greatly increase the clinical value of reserpine or related drugs in the treatment of these disorders.
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PMID:Tetrahydrocannabinol potentiates reserpine-induced hypokinesia. 627 40

Long-term administration of antipsychotics occasionally produces persistent dystonia of the trunk, a disorder known as Pisa syndrome (or pleurothotonus). The development of Pisa syndrome is most commonly associated with prolonged treatment with antipsychotics; however, it has also been reported, although less frequently, in patients who are receiving other medications (such as cholinesterase inhibitors and antiemetics), in those not receiving medication (idiopathic Pisa syndrome) and in those with neurodegenerative disorders. Drug-induced Pisa syndrome predominantly develops in females and in older patients with organic brain changes. It sometimes occurs after the addition of another antipsychotic to an established regimen of antipsychotics or insidiously arises in antipsychotic-treated patients for no apparent reason. The condition generally disappears after antipsychotic drugs are discontinued. Although a pharmacological therapy for drug-induced Pisa syndrome has not been established, we have reported that anticholinergic drugs are effective in about 40% of patients who have episodes of Pisa syndrome with the remaining patients responding to the withdrawal or reduction of daily doses of antipsychotic drugs. The characteristics of its development and prognosis indicate that drug-induced Pisa syndrome consists of two types of dystonia. Some patients develop clinical features of acute dystonia, whereas others develop symptoms similar to tardive dystonia. Like that of tardive dystonia, Pisa syndrome responds better than tardive dyskinesia to a relatively high daily dose of an anticholinergic. However, the significant improvement caused by the withdrawal of antipsychotic drugs in Pisa syndrome differentiates it from tardive dystonia. Thus, Pisa syndrome including these features is considered to be an atypical type of tardive dystonia. These clinical characteristics suggest that the underlying pathophysiology of drug-induced Pisa syndrome is complex. A dopaminergic-cholinergic imbalance, or serotonergic or noradrenergic dysfunction, may be implicated. Asymmetric brain functions or neural transmission may also be considered as underlying mechanisms of the development of Pisa syndrome that is resistant to anticholinergic drugs. Idiopathic Pisa syndrome is characterised by an adult-onset, segmental truncal dystonia in patients with no previous exposure to antipsychotics. It occurs rarely but shows a complete resolution with high doses of anticholinergic drugs.
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PMID:Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. 1188 37

Tissue transglutaminase (tTG) is a marker for apoptosis, and its protein level is known to be increased in post-mortem Alzheimer's and Huntington's disease brains. tTG is increased in the cerebrospinal fluid of patients with Alzheimer's disease. However, the influence of psychotropic medication on acute cell death has not been studied so far in vivo, although some experiments performed in vitro suggest that antipsychotic drugs are neurotoxic. The protein level of tTG was examined in the cerebrospinal fluid obtained from 29 patients under neuroleptic medication in the last 24 h before lumbar puncture (eight patients diagnosed with Alzheimer's disease and 21 patients with other neurological diseases), and compared with those from 55 patients without antipsychotic medication (25 Alzheimer's patients and 30 others). In addition, the influence of several other psychotropic drugs on apoptosis was analysed. A significant influence (P<0.01) of antipsychotic drugs for both the Alzheimer's and the non-Alzheimer's group was found with respect to tTG protein levels in cerebrospinal fluid. By contrast to the male subgroups, the female groups showed a strong influence of neuroleptics on cerebral cell death. Surprisingly, atypical antipsychotics did not differ from typical neuroleptics in neurotoxicity. By contrast, no influence of antidepressants, cholinesterase-inhibitors, nootropics, tranquilizers and tramadol on cerebral cell death was found. The results suggest that typical and atypical antipsychotic drugs may induce cerebral cell death, especially in female patients. Subjects with Alzheimer's disease might be even more vulnerable to any antipsychotic. Therefore, subsequent research should aim to identify atypical neuroleptics without neurotoxicity. A limit on the use of first- and second-generation antipsychotics in elderly patients is proposed. Finally, the possible connection between the observed increased cerebral cell death and tardive dyskinesia, the most threatening side-effect in antipsychotic therapy, is discussed.
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PMID:The influence of psychotropic drugs on cerebral cell death: female neurovulnerability to antipsychotics. 1581 64