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 central cardiovascular effects of a cholinesterase inhibitor, physostigmine, were studied in alpha-chloralose- and urethane-anesthetized cats, to determine the underlying site and mechanism of action. Intravenous injection of physostigmine produced a dose-dependent fall in blood pressure and heart rate. These responses were blocked by intravenous injection of atropine; however, the peripheral antimuscarinic agent, methscopolamine, failed to inhibit the depressor response. In decerebrated cats, physostigmine elicited similar responses in blood pressure and heart rate as in intact animals. In spinal cats, physostigmine failed to evoke any response. Physostigmine significantly reduced sympathetic nervous activity, as measured by renal sympathetic nerve discharges, indicating that the fall in blood pressure was due to a decrease in sympathetic tone. These results demonstrate that physostigmine, which crosses the blood-brain barrier, produces a depressor response through stimulation of muscarinic cholinergic receptors, located in the medullary region and that the effect is mediated by a decrease in sympathetic activity.
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PMID:Central cardiovascular effects of physostigmine in anesthetized cats. 143 99

Physostigmine and other centrally-acting acetylcholinesterase inhibitors are currently being examined for their potential in the treatment of Alzheimer's Disease. The ability to employ this class of agents is limited by the potential for debilitating and dangerous side effects. Clonidine and related drugs have recently been demonstrated to enhance memory performance in monkeys. Clonidine also inhibits the function of cholinergic neurons in specific brain regions and reduces certain side effects of physostigmine. Seven adult macaque monkeys performing a delayed matching-to-sample (DMTS) task received regimens of increasing doses of clonidine and physostigmine on separate occasions to determine the 'best dose' of each agent in terms of enhanced memory performance. The best doses were combined as a single administration and performance compared to that using the two drugs alone. The combination regimen of clonidine and physostigmine was more effective than either drug alone in enhancing memory performance. Part of the benefit may have been due to the ability to employ significantly higher doses of physostigmine in the combination regimen. A single injection of the combination resulted in enhanced performance both on the day of administration as well as on the following day. These results are consistent with the ability of clonidine to limit the expression or intensity of certain physostigmine-induced autonomic side effects, while allowing the cognitive beneficial effects of the cholinesterase inhibitor.
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PMID:Effects of concomitant cholinergic and adrenergic stimulation on learning and memory performance by primates. 161 76

1. Homogenates of tissues from females of the nematode Heterodera glycines were clarified by centrifugation and used to initiate characterization of soluble esterases using p-nitrophenyl acetate as the substrate. 2. Optimum temperature and pH were 40 degrees C and 7.2 respectively. 3. Acetazolamide (a carbonic anhydrase inhibitor) at 10(-3) M did not inhibit enzyme activity, indicating that carbonic anhydrase was not present. 4. Phenamiphos (an organophosphate) at 10(-6) M reduced activity by 38%, whereas eserine hemisulfate (a cholinesterase inhibitor) and aldicarb (a carbamate) were not inhibitory at that concentration, indicating that there was no cholinesterase activity. 5. Eserine hemisulfate, aldicarb, and phenamiphos inhibited enzyme activity by 50% (I50) at 5 x 10(-3) M, 7.5 x 10(-4) M, and 6 x 10(-6) M, respectively. 6. Approximately 25% of the activity detected appeared due to A- and/or C-esterases. 7. The data demonstrated that aldicarb and phenamiphos were active against esterases other than acetylcholinesterase.
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PMID:Partial characterization of soluble esterase from Heterodera glycines and inhibition by aldicarb and phenamiphos. 168 31

The effect of physostigmine, a cholinesterase inhibitor, on the loss of consciousness induced by three different intravenous induction anesthetics, namely midazolam, etomidate and althesin at ED50, was studied in three comparable groups of patients. Ten min before induction, the first and second groups received physostigmine 8 micrograms/kg and 16 micrograms/kg, respectively, and the third group received 2 ml of saline solution. Physostigmine 16 micrograms/kg resulted in a significant decrease in the percentage of unconscious patients with midazolam (from 50% to 10%), but it did not modify the incidence with etomidate or althesin. Physostigmine at doses of 8 micrograms/kg and 16 micrograms/kg could cause 6.7% and 10% nausea, respectively. Although the mechanism of the drug interaction of physostigmine and midazolam is unclear, physostigmine could be used clinically to reverse post-anesthetic somnolence induced by midazolam.
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PMID:Effect of physostigmine on the loss of consciousness induced by midazolam, etomidate and althesin. 175 60

Physostigmine, an acetyl cholinesterase inhibitor, and arecoline, a muscarinic agonist, have been shown to improve Alzheimer presenile dementia in some patients when administered parenterally. Both of these compounds are ineffective orally due to first-pass metabolism. The nasal route was examined as an alternative route of administration for both drugs. Nasal bioavailabilities and dispositions for both drugs were determined in rats. Physostigmine nasal bioavailability was 100% as compared with iv bioavailability, and that of arecoline was 85% when compared with bioavailability following im administration.
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PMID:Intranasal absorption of physostigmine and arecoline. 179 34

To determine the roles of oxidants in airway responsiveness, we studied the effects of the chemical oxidant N-chlorosuccinimide (NCS) on the contractile responses to electrical field stimulation (EFS) and acetylcholine (ACh) in isolated rat tracheal smooth muscle segments. Effects of NCS on the contractile response to EFS (5 Hz, 20 sec of duration, 50 V) reached the maximum with a 60-min incubation time. NCS potentiated the contractile response to EFS, with a maximum effect at 3 x 10(-7) M and to ACh, with a maximum effect at 3 x 10(-6) M. Thus, at a concentration of 3 x 10(-6) M, NCS significantly decreased log ED50 concentration of ACh from a control value of -5.56 +/- 0.05 to -6.24 +/- 0.06. Physostigmine (10(-7) M), at a concentration that did not alter resting tension, mimicked NCS-induced effects on contractile responses to ACh and EFS with the greater degree of shift in the respective dose-response curves. However, NCS failed to alter dose-response curves to carbachol. Removal of the epithelium shifted the dose-response curves to ACh to lower concentrations, but NCS showed similar effects on dose-response curves to ACh with and without the epithelium. Active staining showed that both acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) activities were found in the smooth muscle of the rat trachea. NCS inhibited both enzyme activities from rat tracheal homogenates in a concentration-dependent fashion. These results suggest that NCS potentiates cholinergically induced contraction by decreasing cholinesterase activity and that the oxidation of cholinesterase may cause hyperresponsiveness of airway smooth muscle by inhibition of the enzyme activity.
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PMID:Chemical oxidant potentiates electrically and acetylcholine-induced contraction in rat trachea: possible involvement of cholinesterase inhibition. 192 Jan 23

Physostigmine and tetrahydroaminoacridine (THA) have been reported to improve cognitive function in patients with Alzheimer's disease. Two experiments were conducted to examine the effects of these anticholinesterase agents on learning in aged rats pretreated chronically with barbital. In the first experiment animals received barbital in their drinking water for 46 weeks. Controls were given only water. On days 100-104 of abstinence, when the animals were 20 months old, acquisition of the Morris maze task was initiated after treatment with physostigmine. It was found that physostigmine improved learning of the maze task in control but not barbital treated rats. In the second experiment animals received barbital solution or water as in experiment one. On days 100-103 of abstinence they were injected with THA before being tested in the Morris water maze. It was found that THA improved learning in both barbital treated and control rats. These results corroborate clinical findings of improved cognitive function following treatment with THA, and suggest that the therapeutic effects of THA may be mediated by mechanisms distinct from cholinesterase inhibition. Furthermore chronic barbital treatment could be used as a model to study cognitive disturbances in experimental animals.
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PMID:Learning deficits in aged rats pretreated chronically with barbital and tested late in abstinence: alleviation by tetrahydroaminoacridine. 207 8

Physostigmine is considered to be a potential pretreatment agent against organophosphate intoxication. This investigation elicits the effects of three intensities of acute exercise (50, 80 and 100% VO2max), administration of physostigmine (70 micrograms/kg, i.m.) and the combined effect of physostigmine and three intensities of acute exercise on cholinesterase activity in red blood cells and various tissues and endurance time in rats. The cholinesterase activity in red blood cells in exercised rats not exposed to physostigmine was significantly greater than that of unexercised controls (116, 112 and 108% of control, p less than 0.05, at 50, 80 and 100% VO2max, respectively) while in other tissues the cholinesterase activity in general decreased slightly. In unexercised rats given physostigmine, the cholinesterase activity ranges were 73-79, 66-68, 68-74, 67-81 and 57-61% of controls from 10-30 min in red blood cells, brain, heart, diaphragm and thigh muscle, respectively. In exercised rats exposed to physostigmine, the cholinesterase activity ranges were 54-51, 58-50, 77-73, 71-83 and 54-58% of controls from 10-30 min in red blood cells, brain, heart, diaphragm and thigh muscle, respectively. The results indicate that in control rats not given physostigmine, different intensities of acute exercise affect the cholinesterase enzyme to a moderate degree in red blood cells (p less than 0.05) and heart (p less than 0.05) without affecting brain, diaphragm and thigh muscle. Acute exercise modifies the effect of physostigmine significantly (p less than 0.01) by increasing the cholinesterase inhibition in red blood cells and brain without affecting other tissues. Exposure of rats to physostigmine (70 micrograms/kg, i.m.) increases the endurance time in rats (160-200 g weight), possibly due to peripheral vasodilatation and lowering of core temperature.
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PMID:Interactive effects of physostigmine and exercise on cholinesterase activity in red blood cells and tissues of rat. 209 16

Physostigmine, as a pretreatment candidate for nerve agent poisoning, was examined for cardiopulmonary side effects. Cardiovascular and pulmonary parameters were monitored in unanesthetized domestic pigs which received pulmonary arterial infusion of 5 micrograms/kg/min physostigmine salicylate for 2 hr. A level of 74% inhibition of red blood cell (RBC) acetylcholinesterase (AChE) activity was attained in 45 min, and this level of carbamylation increased only slightly during the remaining infusion period. In addition to this large change in AChE activity, minor changes were observed in hematocrit, heart rate, body temperature, mean aortic pressure, pulmonary arterial wedge pressure, and pulmonary artery pressure. Typically, these parameters showed a trend toward elevated levels. Blood gases, pH, respiratory rate, tidal and minute volume, cardiac output, nonelastic resistance, and dynamic compliance were not significantly different from baseline values. The unanesthetized pig responds to physostigmine in a manner similar to that reported for other species and appears to be a suitable model for evaluating cardiopulmonary effects of cholinesterase inhibitors.
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PMID:Effects of physostigmine on the cardiopulmonary system of conscious pigs. 230 26

Behavioral effects of nicotine and cytisine, and the cholinesterase inhibitors physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (THA), administered intrathecally (IT) at the lumbar level in the rat have been evaluated. Antinociceptive dose relationships were established using the tail immersion test. Total activity, locomotion and rearing were also measured in computerized test boxes. The nicotinic receptor antagonist, mecamylamine, and the muscarinic receptor antagonist, atropine, were used to study the selectivity of the effects. Physostigmine and THA significantly decreased total activity, locomotion and rearing as compared to control animals. The motor effects of physostigmine were completely antagonized only partly. Mecamylamine had no antagonistic effect. Nicotine did not affect any activity parameter. Cytisin reduced total activity and locomotion 1-6 min after dose. IT physostigmine, 15 micrograms, increased tail immersion latency for 30 min. No significant increase in response latency in this test was observed after the IT administration of nicotine or THA, whereas cytisine elicited a small increase. The IT administration of THA, nicotine and cytisine was also associated with gnawing, vocalization and hyperactivity and in the case of THA, diarrhoea. These effects were blocked by mecamylamine. Physostigmine antinociception as well as the behavioral effects including total activity, locomotion and rearing caused by physostigmine and by THA are most probably due to an action on spinal muscarinic receptors. Nicotinic receptors do not seem to be involved in spinal antinociception. Some aversive behavioral effects caused by the IT administration of nicotinic receptor agonists could, however, be attenuated by the spinal administration of the antagonist mecamylamine, which may indicate the involvement of nicotinic receptors in afferent sensory transmission.
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PMID:Behavioral effects after intrathecal administration of cholinergic receptor agonists in the rat. 232 Jul 7


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