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)

The role of hypothermia in the antihypoxic effects of drugs was examined in the present experiments. The effects of environmentally induced hypothermia and drugs were tested by exposing mice to 100% nitrogen gas for 80 sec and counting the number of survivors. In a series of 68 vehicle control groups, the mean of mice surviving the test was 8.6% (SEM = 1.4). Hypothermia induced by lowering the ambient temperature or by isolating mice for a brief period increased the number surviving hypoxia, and the per cent of animals surviving was linearly related to body temperature. When the effects of drugs were compared to that of hypothermia, several drugs were found which protected mice from hypoxia to a greater extent than hypothermia alone. Active substances included the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and diazepam, but not primidone. Physostigmine and the muscarinic agonist oxotremorine also caused significant protection, while the effects of nicotine could be completely accounted for by hypothermia. Arecoline had a biphasic, time-dependent effect that may be explained by a combination of muscarinic and nicotinic actions. The effects of the muscarinic agonists are centrally mediated, since they could be blocked by low doses of scopolamine HCl, but not by the quaternary analog scopolamine methyl nitrate. Furthermore, the antihypoxic effect of physostigmine was not mimicked by the peripherally acting acetylcholinesterase inhibitor, neostigmine. These results suggest that some drugs do have protective effects against hypoxia which are independent of drug-induced hypothermia and that these effects may be mediated through the CNS.
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PMID:Protection against hypoxia-induced lethality in mice: a comparison of the effects of hypothermia and drugs. 359 68

1 Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 mul.2 The topical application of dyflos (1-20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration.3 Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect.4 The two reactivators of acetylcholinesterase, obidoxime (100-200 mg/ml) and pralidoxime mesylate (100-200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect.5 Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied.6 The problem is discussed as to whether the reversal of the dyflos and carbachol-induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine-like action of these compounds or to a combination of both.
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PMID:A central vasodepressor effect of Dyflos. 461 81

A rapid silver nitrate impregnation of nerve fibres has been devised to maintain a histochemically detectable acetylcholinesterase activity at the motor end-plates.
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PMID:A simple silver nitrate impregnation of nerve fibres with preservation of acetylcholinesterase activity at the motor end-plate. 616 Oct 28

The multiplicity of soluble esterases in Raillietina tetragona, R. echinobothrida and R. cesticillus was studied by use of slab polyacrylamide gel electrophoresis. Five fractions of esterase activity were observed in R. tetragona, seven in R. echinobothrida and three in R. cesticillus. The various fractions of esterase activity of closely related species of Raillietina showed differential behaviour towards various chemicals. Based on the inhibitory effect of inhibitors p-CMB, EDTA, malathion, silver nitrate and eserine sulphate, the various esterases have been classified into arylesterase, carboxylesterase, acetylesterase and cholinesterase.
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PMID:A comparative study on esterases from three species of Raillietina. 654 Feb 80

Injection of atropine methyl nitrate or atropine sulphate enhanced the acute thermogenic response to food in rats. The main effector of diet-induced thermogenesis is brown adipose tissue (BAT), but acetylcholine (determined by bioassay) and acetylcholinesterase activity (determined histochemically) were not detected in BAT. This suggests that BAT has no parasympathetic innervation, and atropine must therefore act elsewhere to affect thermogenesis.
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PMID:Parasympathethic effects on diet-induced thermogenesis. 665 75

The levator ani (L. A.) muscle, part of the genital apparatus of rodents, atrophies after castration. Changes in end-plate structure in the L. A. muscle of castrated male rats were examined with correlated light and electron microscopic methods. Four months after castration acetylcholinesterase staining reveals, in some muscle fibres, the presence of subneural gutters composed of a succession of cuplets whereas the subneural gutters are continuous and ramified in control muscles. Six months after castration most of the end-plates are further modified. Their terminal arborization, as revealed by silver nitrate staining, is more tortuous and irregular than in controls. At the ultrastructural level, reduced sole-plate and superimposed axonal endings are seen in some end-plates three months after castration. Our findings demonstrate that the changes (reduction of muscular activity and atrophy of muscle) are accompanied by adaptations of the neuromuscular junctions. As receptors for testosterone are known to be present in these motoneurons and muscle fibres, the observed morphological changes might be under the control of testosterone acting on both muscle and motoneurons.
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PMID:Effect of castration on the morphology of the motor end-plates of the rat levator ani muscle. 706 6

The effects of hemicholinium-3 (HC-3) or 4-(l-naphthylvinyl)pyridine (4-NVP) alone and together with cholinolytics and/or cholinesterase inhibitors on brain acetylcholine (ACh) levels and survival were studied. Intracerebroventricular (ICVT) injection of 10 micrograms HC-3 280 min before euthanasia by microwave irradiation reduced rat cerebral ACh levels from 28.4 to 5.4 nmoles ACh/g wet tissue. In rats pretreated with HC-3 alone or with other pretreatment drugs prior to giving up to 2.7 LD50 of soman, iv, cerebral ACh levels increased very little, but in animals not receiving HC-3, brain ACh levels increased to 67.1 nmoles. Treatment of unpoisoned rats with 4-NVP resulted in a significant (26%) reduction in ACh. The inclusion of atropine with 4-NVP caused sign-free doses of physostigmine to produce toxic signs in rabbits and did not enhance the efficacy of carbamate pretreatment against soman. Pretreatment of rabbits with pyridostigmine and atropine methyl nitrate (AMN) failed to provide any protection against soman, but when HC-3, ICVT, was included with those drugs, the protective ratio (PR), against soman was increased excess ACh is a primary lesion in organophosphorus anticholinesterase intoxication and that the central nervous system is quite sensitive to excesses of ACh.
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PMID:Effects of inhibitors of acetylcholine synthesis on brain acetylcholine and survival in soman-intoxicated animals. 710 25

Bilateral olfactory bulbectomy produced the increased tendency of mouse-killing behavior in nonkiller rats (60% on the 14th day after surgery). Scopolamine hydrobromide (4 and 8 mg/kg, IP) significantly suppressed the killing response in a dose-dependent manner, whereas methylscopolamine nitrate was ineffective. In order to investigate a possible neural mechanisms, choline acetyltransferase (CAT) and acetylcholinesterase (ACh-E) activities were measured in 7 discrete brain areas: cortex, amygdala, hypothalamus, thalamus, tegmentum, hippocampus, and pons plus medulla oblongata. Although the central anticholinergic drug suppressed mouse-killing, no significant difference in either CAT and ACh-E activities was found between the killer and nonkiller rats in any of the brain areas determined in this study. The evidence suggests that the neurochemical findings may not fit the pharmacological findings for supporting a unified cholinergic hypothesis for mouse-killing behavior.
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PMID:Regional changes in brain cholinergic enzyme activities after bilateral olfactory bulbectomy in relation to mouse-killing behavior by rats. 719 71

These experiments studied the effect of scopolamine on memory formation and subsequent memory recall. Different groups of rats were trained on a Y-maze brightness discrimination task 20 min after IP injection of 2 mg/kg scopolamine HBr, an anticholinergic. Retention tests were then conducted 1 day or 2, 4, or 6 weeks after training. Deficits in retention performance were observed at 1 day and 2 weeks after training but not at the longer intervals. In addition, other rats were trained in the same manner and after the same dose of scopolamine but were then retention tested 20 min after 0.5 mg/kg physostigmine salicylate, a cholinesterase inhibitor. These subjects also showed deficits at 1 day and 2 weeks but were not different from controls at the longer intervals. Amnesia was not, however, produced after treatment with scopolamine methyl nitrate or by injections of scopolamine HBr administered immediately after training. These results suggest that scopolamine, present in the central nervous system during training or within the first few moments thereafter, modifies the formation of the memory trace in such a way that memory is not available for recall for a period of weeks.
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PMID:Time dependent changes in anterograde scopolamine-induced amnesia in rats. 723 57

The purpose of this investigation was to compare the efficacy of diazepam and a water soluble pro-diazepam drug, avizafone (lysyl, peptido-aminobenzophenone diazepam pro-drug) in preventing or reducing the severity of soman-induced neuropathology in rats and to determine the temporal relationship between seizure initiation, anticonvulsant administration and the incidence and severity of soman-induced neuropathology. Brains from rats, treated with a convulsant dose of soman (pinacolyl methylphosphonofluoridate) and anticonvulsants such as diazepam and avizafone, were evaluated by light microscopy for evidence of neuropathology. All rats received atropine methyl nitrate (20 mg/kg, ip)+the bispyridinium acetylcholinesterase reactivator HI-6 (125 mg/kg, ip; 1-(((4-(aminocarbonyl)pyridinio) methoxy)methyl)-2-((hydroxyimino)methyl)-pyridinium dichloride) in the same solution 10 min before soman (130 micrograms/kg,sc). Three days later the rats were perfused and the tissue fixed for histological evaluation. Necrosis and/or malacia (degenerative changes) and hemorrhage were observed in some groups. The sites where pathology was most frequently observed and with greater severity were the piriform cortex, amygdala and (dorsal) thalamus. Less severe changes were observed in the cerebral cortex and hippocampus. There were no changes in the hypothalamus. Diazepam given 10 minutes before soman prevented the occurrence of soman-induced convulsions and neuropathology (i.e. degenerative changes were not then seen). Diazepam given at the start of the soman-induced convulsions reduced considerably the convulsions and the degree of neuropathology. Avizafone given 10 minutes before soman reduced slightly the effect of soman. Other treatments (diazepam given 30, 60 and 120 minutes after the start of the convulsions and avizafone given at the start of convulsions) showed little or no effect on the neuropathology associated with soman administration. The results of this study have demonstrated that the use of an anticonvulsant, such as diazepam, must be initiated shortly after soman exposure in order for any therapeutic benefit to be realized.
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PMID:Efficacy of diazepam and avizafone against soman-induced neuropathology in brain of rats. 816 92


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