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)

Rat lines were selected by breeding for sensitivity to signs of autonomic stimulation (hypotherma, loss of body weight, and reduced water intake) induced by the cholinesterase inhibitor diisopropyl fluorophosphate (DFP). These lines have since been maintained for 10 generations by continued selection for hypothermic responsiveness to the muscarinic agonist oxotremorine. The sensitive rats (Flinders Sensitive Line, FSL) differ from the resistant rats (Flinders Resistant Line, FRL) both neurochemically and behaviorally, particularly in aversively motivated test situations in which response speed is assessed. This study was conducted to determine whether the selected differences in cholinergic autonomic sensitivity would be expressed as differences in cognitive ability based on choice accuracy in appetitive tasks. The working and reference memory of rats of these two strains was thus assessed using operant delayed matching-to-position/visual discrimination (DMTP/VD) and the radial-arm maze. A Long-Evans (L-E) reference group was included in the DMTP/VD study. FSL rats responded more slowly than the other rats during acquisition of both tasks, but showed no differences in response accuracy either during acquisition or during asymptotic performance of either task. In addition, challenges with muscarinic and nicotinic antagonists and agonists [scopolamine (0.06-1.0 mg/kg), pilocarpine (1.0-4.0 mg/kg), mecamylamine (1.0-10.0 mg/kg), and nicotine (0.1-0.3 mg/kg)] demonstrated predicted differences in sensitivity among the lines only on performance measures such as response latency and trial completion. Counter to prediction, the sensitivity of the FRL rats to the ability of scopolamine to reduce matching accuracy was lower than those of the L-E and FSL rats. Thus selection based upon physiological endpoints related to cholinergic autonomic homeostasis did not produce analogous differences in cognitive function in rats.
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PMID:Spatial working and reference memory in rats bred for autonomic sensitivity to cholinergic stimulation: acquisition, accuracy, speed, and effects of cholinergic drugs. 766 85

In recent years muscarinic receptor agonists and cholinesterase inhibitors have been developed for the treatment of Alzheimer's disease. We have evaluated examples from both classes of compounds in rodent tests of reference and working memory, as well as tests that are sensitive to the side-effects of these compounds. Thus, three selective muscarinic receptor partial agonists L-689,660, (M1/M3), AF102B (M1/M3) and L-687,306 (M1) and two cholinesterase inhibitors, E2020 and eptastigmine, were compared in a mouse tail-flick (TF) test, a rat response sensitivity (RS) test, in rat tests of reference memory, passive avoidance (PA) or conditioned suppression of drinking (CSD), and working memory (delayed-matching-to-position, DMTP). In the TF test, all of the compounds tested, with the exception of L-687,306, (1.0-30.0 mg/kg) dose-dependently induced antinociception of which L-689,660 was the most potent (minimum effective dose (MED) = 0.03 mg/kg). In the RS test, all of the compounds, but again with the exception of L-687,306, (1.0-30.0 mg/kg), dose-dependently reduced response rates, of which L-689,660 was again the most potent (MED = 0.1 mg/kg). In the reference memory test, all the compounds reversed the effects of a scopolamine-induced deficit with L-687,306 being the most potent (MED = 0.01 mg/kg). By contrast, in the DMTP test, although both the cholinesterase inhibitors and L-687,306 reversed the effects of scopolamine-induced deficit, L-689,660 and AF102B were without effects. These results suggest that cholinesterase inhibitors and low efficacy M1 selective muscarinic receptor agonists can reverse the effects of a scopolamine-induced deficit in animal tests of reference and working memory at doses that do not induce the side-effects usually associated with cholinomimetics.
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PMID:The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory. 811 20

We report a 60-yr-old woman with schizophrenia, who manifested a neuroleptic malignant (NM)-like syndrome after acute organophosphate poisoning (OPP). She attempted suicide by ingesting 40% emulsions of DMTP (S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadizol-3-yl-methyl O,O-dimethyl phosphorodithioate) 100 ml. On admission, she was unconscious and demonstrated convulsions, depressed respiratory movements, miosis and profuse salivation. Plasma cholinesterase concentration (842 IU.L-1) was very low and OPP was diagnosed. She was treated with gastric lavage, atropine and pralidoxime (PAM). By the seventh day after admission, symptoms of OPP disappeared and serum ChE had recovered to a sub-normal level. On the 13th day, she demonstrated coma, high fever (41.0 degrees C) and lead-pipe rigidity. Serum CPK was increased (1631 IU.L-1). Dantrolene sodium iv was administered for three days. Body temperature began to decrease in 24 hr, and her consciousness, muscle rigidity and other neurological symptoms returned to normal by the 16th day after admission. She was discharged from the hospital without sequelae 55 days after admission. We conclude that OPP can predispose to an NM-like syndrome and that dantrolene may be effective in the management.
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PMID:Neuroleptic malignant-like syndrome: a complication of acute organophosphate poisoning. 859 Apr 92