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)

Bilateral ibotenic acid injections aimed at the entorhinal cortex (EC) lesioned the EC and subiculum in 30% of animals (group EC/S) and caused additional hippocampal damage in 50% (group RH). Both lesions increased acetylcholinesterase (AChE) staining in the intermediate molecular layer of the dentate gyrus. EC/S lesions increased diurnal deep sleep and the incidence of spindles but decreased REM sleep. RH lesions increased nocturnal deep sleep and decreased nocturnal quiet sleep. Both lesions reduced power over the theta frequency range from 6-10 Hz for epochs of REM sleep and quiet waking but not deep sleep. Peak frequency was unaffected. The RH group and a subset of the EC/S group were nocturnally, but not diurnally, hyperactive. Six weeks after the lesion there was no evidence for hyperactivity in a novel open field. The EC/S lesion impaired exploration as indicated by reduced motility and rearing in an open field and by the failure of EC/S-lesioned rats to increase contact time in response to a novel olfactory cue. Place navigation learning in a Morris maze was not affected by EC/S or RH lesions. However, when the spatial location of the hidden platform was shifted EC/S-lesioned rats were impaired. The sprouting response, reduced theta power and exploration deficits resemble those reported following electrolytic lesions, but the lack of effect on place navigation learning contrasts with reports of impaired spatial learning following electrolytic lesions. The data prompt a reexamination of the role which the EC projection to the hippocampus plays in spatial learning.
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PMID:Behavioural and electrophysiological studies of entorhinal cortex lesions in the rat. 134 67

Since REM sleep deprivation was reported to increase the activity of acetylcholinesterase, an attempt was made to investigate whether the different forms of enzyme could be affected selectively. The flower pot method was used for deprivation and suitable control experiments were conducted. The bound and the soluble forms, if affected would show an increase or a decrease, respectively, on REM deprivation. The former is affected first in the pons while the latter in the medulla. The findings support the pontomedullary cholinergic mechanism for the generation of REM sleep. Though there may be a possibility of conversion of the free to the bound form, the increase in the latter was more than the decrease in the former.
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PMID:Effect of REM sleep deprivation on molecular forms of acetylcholinesterase in rats. 152 Aug 54

In this experiment, rats were treated chronically with moderate doses of the acetylcholinesterase inhibitor di-isopropyl-fluorophosphate (DFP). After an initial injection of 1.0 mg/kg DFP, the rats received a 0.5 mg/kg injection every third day thereafter for a total of 5 injections (13 days). Following the treatment regimen, the rats were found to have increased amounts of REM sleep compared to vehicle control rats. The time spent awake and in slow wave sleep was relatively unaffected. The increase in REM sleep appears to be due to increased numbers of REM sleep episodes and not an increase in the average length of the REM sleep episodes. Furthermore, the increased REM sleep does not appear to be due to REM rebound or to disruptions of circadian rhythm.
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PMID:The acetylcholinesterase inhibitor di-isopropyl-fluorophosphate increases REM sleep in rats. 409 83

To date it has not been established whether the anticholinergic properties of imipramine are responsible for the drug's suppresion of REM and prolongation of REM induction. A cholinesterase inhibitor, physostigmine, was administered in conjunction with imipramine to determine if these effects of imipramine were cholinergically medicated. Sleep EEG recordings were observed in rats administered either physostigmine (1.0 mg/kg), or imipramine (1.25, 2.5 or 5.0 mg/kg), alone or in combination. The results indicate that physostigmine blocks the effects of imipramine on REM latency.
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PMID:Imipramine and REM sleep: cholinergic mediation in animals. 677 26

1. Effect of REM sleep (REMs) deprivation treatment on clozapine response in the forced swimming test was investigated. 2. Clozapine significantly increased the swimming activity in REMs-deprived mice at a dose of 5 mg/kg (i.p.) which did not affect the activities in the control groups. 3. Physostigmine (0.3 mg/kg, i.p.), an acetylcholinesterase inhibitor, blocked the increasing effect of 5 mg/kg clozapine on swimming activity in REMs-deprived animals. 4. These results suggest that the REMs deprivation treatment-induced enhancement of effect of clozapine on swimming activity is mediated by the functional change of central cholinergic system following the treatment.
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PMID:REM sleep deprivation treatment enhances the effect of clozapine in the forced swimming test. 759 Jan 10

Intracerebroventricular injection of the toxin 192 IgG-saporin (4 micrograms) kills the cholinergic neurons of the basal forebrain bearing the low affinity NGF receptor (NGFr). The effect of this cholinergic denervation on the hippocampal and cortical electrical activity (EEG) was studied during sleep and wakefulness. EEG was recorded under freely-moving conditions in lesioned (n = 10) and control (n = 6) rats (8-16 days post-injection). In lesioned rats, active (AW) and quiet (QW) wakefulness episode durations were similar to those of controls whereas the REM sleep duration was reduced, 8 days post-lesion (P < 0.01). Bouts of REM sleep were more numerous but shorter. The hippocampal theta activity was still present in lesioned-rats during AW (type 1 theta), QW (type 2 theta) and REM sleep. The frequency was unchanged but the amplitude of the three types of theta was significantly reduced (P < 0.01). Type 2 theta occurred with shorter and less regular bouts (P < 0.05). Abnormal slow waves (2-4 Hz) were observed during wakefulness. Histology showed a dramatic loss of NGFr-positive neurons in the basal forebrain and a decline in hippocampal and cortical acetylcholinesterase activity. These results suggest that the cholinergic septohippocampal input is not the primary pacemaker for the hippocampal theta rhythm.
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PMID:Selective immunolesion of the basal forebrain cholinergic neurons: effects on hippocampal activity during sleep and wakefulness in the rat. 760 Jan 85

The pharmacological and clinical properties of a novel phenyl carbamate acetylcholinesterase (AChE) inhibitor, SDZ ENA 713 are described. In animals and human subjects this compound showed superior chemical stability, oral bioavailability and a longer duration of action than physostigmine. SDZ ENA 713 produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than in the heart and skeletal muscle, which explains its relatively low toxicity and freedom from cholinergic side effects. The selective effect in the cortex and hippocampus may be due to its preferential inhibition of the G1 form of the enzyme, which is present in relatively higher concentrations in these brain areas. Evidence of a selective hippocampal action was obtained in normal human subjects in whom REM sleep density was increased at doses that had no effect on plasma cholinesterase. If memory impairments in AD are related to a lack of cholinergic activity in cortical and hippocampal brain areas, SDZ ENA 713 should produce significant symptomatic improvement.
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PMID:Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors. 788 3

The present study investigated the impact of the cholinesterase inhibitor tetrahydroaminoacridine (THA; tacrine) on sleep in healthy subjects. According to the reciprocal interaction model of non-rapid eye movement (NREM) and REM sleep regulation, which postulates a primary role in cholinergic neurotransmission for the initiation and maintenance of REM sleep, it was expected that THA would lead to an earlier onset of REM sleep. In 12 healthy subjects aged from 21 to 50 years two different doses (20 mg, 40 mg) were administered 1 hour prior to bed time and compared to placebo. Only the higher dose of THA significantly shortened REM latency. No other significant effects on sleep architecture were observed, although administration of 40 mg tacrine was associated with a decrease in sleep efficiency and a prolongation of sleep latency. Blood plasma levels of tacrine and its metabolite 1-hydroxytacrine measured prior to sleep and during the first 90 min of sleep were significantly correlated with the onset of REM sleep in relation to the timing of drug administration (only for the 20 mg dose). The reversible cholinesterase inhibitor THA exerts effects on REM latency comparable to those observed with other cholinomimetic agents.
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PMID:Effect of tetrahydroaminoacridine on sleep in healthy subjects. 873 20

Cholinergic stimulation in the basal forebrain (BF) triggers cataplexy in canine narcolepsy. Extracellular single unit recordings in the BF were carried out in freely moving narcoleptic dogs to study the neuronal mechanisms mediating cataplexy induction in the BF. Among the 64 recorded neurons, 12 were wake-active, three were slow wave sleep (SWS)-active, 17 were wake-/REM-active, 11 were REM sleep-active, three were cataplexy-active, and the other 18 were state-independent. Systemic administration of physostigmine, a cholinesterase inhibitor, induces status cataplecticus, decreases SWS and increases acetylcholine levels in the BF. Firing of most of the state-dependent neurons in the BF was significantly modified by physostigmine. Some of these neurons may thus mediate sleep stage changes or the effect on cataplexy observed after cholinergic stimulation in the BF.
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PMID:Neuronal activity in the cholinoceptive basal forebrain of freely moving narcoleptic dobermans. 985 75

Previous research has shown that acetylcholinesterase inhibitors may affect REM sleep, however, results are inconclusive. From the present findings it is concluded that the effects of rivastigmine, a reversible acetycholinesterase inhibitor, on REM sleep are more pronounced in the elderly where we found REM latency to be significantly reduced. This may be explained by better bioavailability and/or by reduced stability of the circadian rhythmicity in elderly individuals. Because rivastigmine is used in the treatment of Alzheimer's disease, further research investigating the relationship between the REM enhancing properties of rivastigmine and cognitive functioning seems promising.
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PMID:The effect of rivastigmine on sleep in elderly healthy subjects. 1076 83


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