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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intracerebroventricular (i.c.v.) injection of physostigmine and hemicholinium-3 (HC-3) on reflex bradycardia and tachycardia have been studied in unanesthetized rats. The reflex increases and decreases in heart rate were elicited by i.v. injection of norepinephrine and sodium nitroprusside, respectively. Physostigmine (5-10 micrograms) increased basal mean arterial pressure (MAP), reduced basal heart rate (HR), enhanced the reflex bradycardia and reduced reflex tachycardia. Physostigmine did not modify either the pressor effect of norepinephrine, the depressor effect of sodium nitroprusside or the responsiveness of peripheral muscarinic receptors. Pretreatment (i.c.v.) with atropine (0.3 micrograms) completely abolished the effect of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. Pretreatment (i.c.v.) with mecamylamine (50 micrograms) did not modify the effect of the cholinesterase inhibitor on MAP, HR and reflex tachycardia, but inverted its effect on reflex bradycardia. Injection of HC-3 (20 micrograms i.c.v.) did not modify MAP, but reduced HR and inhibited both reflex bradycardia and reflex tachycardia. The HC-3 bradycardic effect started within minutes and lasted for about 1 hr, while the depressor effect on the reflexes began only after 15 min and continued for several hours. In addition, i.c.v. pretreatment with HC-3 completely abolished all the effects of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. These results suggest that brain acetylcholine has a modulatory effect on baroreceptor reflexes. This modulation operates through muscarinic receptors in reflex tachycardia and through both muscarinic and nicotinic receptors in reflex bradycardia.
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PMID:Modulatory effect of brain acetylcholine on reflex-induced bradycardia and tachycardia in conscious rats. 744 97

One consistent finding in senile dementia of the Alzheimer's type is that the brain has reduced ability to synthesize acetylcholine. This has been related, in part, to memory dysfunctions. Although a cholinergic deficit is not singularly responsible for symptoms of dementia, treatment strategies have been designed to facilitate cholinergic activity by inhibiting acetylcholinesterase (AChE). To minimize toxicity, however, a cholinesterase inhibitor selective for only AChE would be an ideal treatment. The purpose of this study was to determine the selectivity of physostigmine, metrifonate, methanesulfonyl fluoride and tetrahydroaminoacridine (tacrine) toward AChE as compared with butyrylcholinesterase (BChE) in human cortex. The results show that methanesulfonyl fluoride is selective as an inhibitor of AChE as compared with BChE. Physostigmine inhibited AChE more than BChE. Metrifonate was found to inhibit BChE more than AChE. Tetrahydroaminoacridine inhibited both enzymes in a complex way.
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PMID:Cholinesterase inhibitors proposed for treating dementia in Alzheimer's disease: selectivity toward human brain acetylcholinesterase compared with butyrylcholinesterase. 763 41

A regime was developed, using mini-osmotic pumps, for the continuous subcutaneous administration of low doses of physostigmine (12.1, 9.7, 4.85 and 2.43 micrograms h-1), in combination with hyoscine (1.94 or 0.39 micrograms h-1), to guinea-pigs for up to 13 days. Physostigmine, in combination with hyoscine, inhibited plasma cholinesterase, and red blood cell and brain acetylcholinesterase, in a concentration-dependent manner, did not affect the normal growth rate of guinea-pigs, and produced no obvious signs of poisoning. A dose rate of 4.85 micrograms h-1 physostigmine and 1.94 micrograms h-1 hyoscine was required to inhibit red cell acetylcholinesterase by 30% and brain acetylcholinesterase by 5-15%, with an accompanying plasma hyoscine concentration of 700-850 pg mL-1. There was an apparent decline in red cell acetylcholinesterase activity during the 13 days. Hyoscine levels were higher in the cholinergic-rich areas of the brain than in the plasma. Continuous pretreatment (1 or 6 days) with physostigmine (4.84 micrograms h-1) and hyoscine (1.94 micrograms h-1) provided complete protection against the lethal effects, and minimized the incapacitation and weight loss produced by soman at a dose equivalent to the LD99 value. Following soman challenge, guinea-pigs exhibited early signs of soman poisoning, but generally these signs of poisoning were minimal by 1-2 h. Extending the pretreatment time to 13 days protected 75% of the guinea-pigs against the lethal effects of soman poisoning. Red cell acetylcholinesterase activity, 24 h after soman poisoning, was higher following continuous pretreatment with physostigmine and hyoscine than after acute treatment with atropine.
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PMID:Continuous administration of low dose rates of physostigmine and hyoscine to guinea-pigs prevents the toxicity and reduces the incapacitation produced by soman poisoning. 771 14

Facial electromyography (EMG) coupled with visual observation was used to investigate spontaneous and drug induced perioral movements in freely moving rats. Four separate perioral behaviours were identified; facial tremor, purposeless chewing, gaping and yawning. Facial tremor, yawning and gaping but not purposeless chewing produced characteristic EMG signals. Normal rats displayed a low level of purposeless chewing, occasional bursts of facial tremor but not gaping or yawning. Each burst of facial tremor was accompanied by a transient increase in purposeless chewing. Administration of the D1 agonist SKF 38393 induced a dose related increase in bursts of facial tremors and consequently an increase in the total number of purposeless chews. Gaping and yawning were not induced by SKF 38393 administration. Administration of the cholinesterase inhibitor physostigmine (0.1-0.4 mg/kg) induced a dose related increase in the total number of purposeless chews, but primarily these were not associated with facial tremor. Administration of physostigmine also increased gaping and yawning. Administration of the D1 antagonist SCH 23390 almost abolished facial tremor in normal treated rats but only partially reduced that induced by SKF 38393 and physostigmine. SCH 23390 reduced purposeless chewing in SKF 38393 treated rats but not in normal or physostigmine treated animals. Administration of the cholinergic antagonist atropine almost abolished facial tremor in normal and physostigmine treated rats, but only reduced by 46% that induced by SKF 38393. Atropine reduced purposeless chewing in normal, physostigmine and SKF 38393 treated animals. Physostigmine induced gaping and yawning were abolished by atropine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electromyographical differentiation of the components of perioral movements induced by SKF 38393 and physostigmine in the rat. 787 Oct 53

The effects of i.c.v. injection of the mu-selective opioid receptor agonist DAMGO and the effects of its combination with the endogenous kappa-opioid receptor agonist dynorphin A-(1-13) on memory processes were examined in mice, using spontaneous alternation performance associated with working memory in a Y-maze. DAMGO (10 and/or 30 ng) impaired spontaneous alternation performance and increased total arm entries, which are considered to reflect locomotor activity. beta-Funaltrexamine (5 micrograms, i.c.v.), a mu-selective opioid receptor antagonist, almost completely antagonized the impairment of alternation performance induced by DAMGO (10 ng). Physostigmine (0.1 mg/kg, i.p.), a cholinesterase inhibitor, improved the DAMGO (10 ng)-induced impairment of alternation performance. Dynorphin A-(1-13) (1, 3 and 10 micrograms, i.c.v.) alone was without significant effects on alternation performance. On the other hand, dynorphin A-(1-13) (3 and 10 micrograms) significantly improved the impairment of spontaneous alternation performance induced by DAMGO (10 ng). The effects of dynorphin A-(1-13) (3 micrograms) on the DAMGO-induced impairment of spontaneous alternation were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid receptor antagonist. The present results demonstrate that DAMGO impairs alternation performance by activating mu-opioid receptors, whereas dynorphin A-(1-13) attenuates the DAMGO-induced impairment of alternation performance through the mediation of kappa-opioid receptors. These findings suggest that mu- and kappa-opioid systems are fully involved in memory function and have opposite effects on spontaneous alternation performance as it is reflected by working memory in mice.
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PMID:Dynorphin A-(1-13) potently improves the impairment of spontaneous alternation performance induced by the mu-selective opioid receptor agonist DAMGO in mice. 790 56

This study was undertaken to investigate the possibility that non-cholinergic mechanism accounts for acute lethality of cholinesterase (ChE) inhibitor. Physostigmine and carbamate insecticides (2-s-butylphenyl methylcarbamate (BPMC); isoprocarb, 2-isopropylphenyl methylcarbamate (MIPC); and propoxur, 2-isopropoxyphenyl methylcarbamate (PHC)) were employed as ChE inhibitors. Rabbits intravenously given any of the ChE inhibitors showed typical signs of anti-ChE poisoning, a marked inhibition of systemic ChE activity, and an increase in RR interval on an ECG. Injection of physostigmine or PHC at a lethal dose produced a pressor response before cessation of spontaneous breathing. In contrast, injection of MIPC or BPMC primarily elicited a cardiovascular collapse, characterized by a rapid and progressive decrease in blood pressure and a decrease in QRS amplitude of ECG, before cessation of spontaneous breathing. The atropine pretreatment inhibited the pressor response, but not the depressor response and the QRS change. The pretreatment antagonized acute lethality of the ChE inhibitors except BPMC. It is suggested that the mode of lethality for intravenous ChE inhibitor could be determined by a balance between anti-ChE activity and some mechanism other than ChE inhibition. BPMC produced acute lethality through the latter mechanism rather than the former one.
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PMID:Non-cholinergic lethality following intravenous injection of carbamate insecticide in rabbits. 797 14

Effects of central administration of a cholinesterase inhibitor, physostigmine, on cardiovascular responses to static contraction and passive stretch of the triceps surae were studied using anesthetized cats. Contraction increased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) by 44 +/- 5 mmHg, 18 +/- 1 beats/min, and 86 +/- 6%, respectively. MAP, HR, and RSNA increased during stretch by 44 +/- 5 mmHg, 15 +/- 1 beats/min, and 61 +/- 4%, respectively. Administration of physostigmine (100 micrograms; 5 microliters) into the third ventricle decreased resting MAP by 22 +/- 3 mmHg and RSNA by 32 +/- 4%, with no effect on HR. Physostigmine attenuated the contraction-evoked responses as MAP, HR, and RSNA increased by 17 +/- 2 mmHg, 3 +/- 1 beats/min, and 31 +/- 6%, respectively. Also, physostigmine blunted MAP, HR, and RSNA responses to stretch (16 +/- 2 mmHg, 4 +/- 1 beats/min, and 9 +/- 6%, respectively). Posterior hypothalamic stimulation increased MAP by 39 +/- 3 mmHg, which was unaffected by physostigmine, despite a lower baseline. Cardiovascular and RSNA responses to contraction and stretch returned to control 90-120 min after physostigmine. Preadministration of the muscarinic antagonist, atropine sulfate (100 micrograms; 5 microliters), blocked the effects of physostigmine. Results suggest central cholinergic stimulation can inhibit the exercise pressor reflex in anesthetized cats.
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PMID:Central cholinergic modulation of the exercise pressor reflex in anesthetized cats. 804 74

Two of the more consistent findings in Alzheimer's disease are depressions in frontal and temporoparietal glucose metabolism and a loss of cholinergic neurons in the nucleus basalis of Meynert. Nonetheless, cholinergic replacement strategies have had only minimal therapeutic successes. Whether this situation reflects the limited contribution of cholinergic deafferentation to the intellectual decline or the meager ability of the pharmaceuticals tested to exert their intended pharmacologic action remains unclear. To address this question, the distribution of cerebral abnormalities found in untreated Alzheimer patients, as revealed by positron emission tomography following 18F-fluorodeoxyglucose, were compared with the pattern of functional changes produced by drugs that block or stimulate cholinergic function. Physostigmine was administered to 6 Alzheimer patients to increase brain cholinergic neurotransmission. The anticholinergic scopolamine, given to normal volunteers, was administered to 6 age-matched controls. These data were compared to those obtained from the same subjects while receiving placebo. Amnestic doses of the anticholinergic, scopolamine increased glucose metabolism by up to 20% (p < 0.001) in all brain regions studied, except thalamus. This response contrasted with the metabolic reductions of up to 17% (p < 0.01), especially in parietal and frontal association cortices, occurring in unmedicated Alzheimer patients. Maximum tolerated doses of the anti-cholinesterase, physostigmine, rather than tending to normalize abnormalities in these patients, further reduced cerebral metabolism (p < 0.01) and increased metabolism in thalamus in a pattern inversely correlated (p < 0.001) with that produced by scopolamine. These results fail to support a cholinergic basis for the abnormal metabolic pattern in Alzheimer's disease.
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PMID:Metabolic effects of scopolamine and physostigmine in human brain measured by positron emission tomography. 806 20

Cholinomimetic agents increase blood pressure and heart rate via central muscarinic cholinoceptors in various species. It was reported that i.c.v. injection of the muscarinic M1 and M3 cholinoceptor selective antagonist, 4-DAMP (4-diphenylacetoxy-N-methyl-piperidine methiodide), inhibited the pressor response to physostigmine, while the M1 selective antagonist, pirenzepine, was ineffective. In the present study, the involvement of muscarinic M2 cholinoceptors in central cholinergic hypertension and tachycardia was investigated. Physostigmine (10-80 micrograms/kg i.v.), a cholinesterase inhibitor, and oxotremorine (20-40 micrograms/kg i.v.), a direct muscarinic cholinoceptor agonist, caused a dose-dependent increase in blood pressure. Additionally, physostigmine induced dose-dependent tachycardiac responses. I.c.v. administration of the muscarinic M2 cholinoceptor antagonists, AF-DX 116 and methoctramine, inhibited both physostigmine (60 micrograms/kg) and oxotremorine (20 micrograms/kg)-induced pressor responses at their lower doses used in this study (100 nmol/rat and 10 nmol/rat, respectively). These findings indicate the partial involvement of postsynaptic muscarinic M2 cholinoceptors. The higher doses of the antagonists (AF-DX 116,300 nmol/rat and methoctramine 30 nmol/rat) potentiated the blood pressure increase due to physostigmine but did not affect that due to oxotremorine. The physostigmine-induced tachycardiac responses were influenced similarly by these antagonists. These results suggest the presence and tonic influence of presynaptic inhibitory muscarinic M2 cholinoceptors.
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PMID:Central muscarinic M2 cholinoceptors involved in cholinergic hypertension. 811 94

The present study compares the effects of two cholinesterase inhibitors, tetrahydroaminoacridine (THA, 1 and 3 mg/kg) and physostigmine (0.12 and 0.36 mg/kg), on spatial navigation (water maze, WM) and avoidance (step through passive avoidance, PA) performance. THA and physostigmine did not facilitate WM or PA performance in control or p-chlorophenylalanine (PCPA)-treated rats. THA at 3 mg/kg, but not at 1 mg/kg, completely restored the defect in WM and PA performance in rats pretreated with 7.5 mg/kg mecamylamine, a centrally active nicotinic antagonist. Physostigmine completely restored behavior in WM and PA tests at 0.12 and 0.36 mg/kg in mecamylamine-treated rats. In rats pretreated with mecamylamine+PCPA, 3 mg/kg THA to some extent restored WM performance but had no effect on PA retention. Likewise, physostigmine partially restored WM performance but did not facilitate PA retention in mecamylamine+PCPA-pretreated rats. The present study suggests that serotonergic dysfunction may decrease the efficacy of cholinesterase inhibitors to reverse the defect in WM and PA behavior occurring as a consequence of a decrease in activity of nicotinic-mediated functions.
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PMID:Effects of THA and physostigmine on spatial navigation and avoidance performance in mecamylamine and PCPA-treated rats. 830 18


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