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)

The acute effects of the organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman (180 micrograms/kg, s.c.; equivalent to 1.6 x the median lethal dose) that produced 100% convulsions. Signs of intoxication as well as the time-to-onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 mumol/kg for scopolamine HBr, biperiden, trihexyphenidyl, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order of potency for inhibition of hypersecretions among these compounds was observed. Parallel studies with quaternary analogs of atropine sulfate and scopolamine HBr demonstrated, however, that these charged compounds afford no protection against soman-induced hypersecretions and convulsions. The results indicate that tertiary anticholinergic compounds afford protection against soman-induced convulsions and hypersecretions and that the beneficial anticonvulsant effects are mediated through the central cholinergic system. Excitatory amino acid neurotransmitter systems may be involved in the effectiveness of these compounds.
 ...
PMID:Anticonvulsant actions of anticholinergic drugs in soman poisoning. 191 66

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.
 ...
PMID:Time dependent changes in anterograde scopolamine-induced amnesia in rats. 723 57

The effects of the muscarinic antagonists, scopolamine HBr and MeBr, a cholinesterase inhibitor, E2020, and K+ channel blockers, 4-aminopyridine (4-AP) and apamin, on the performance of rats in a delayed matching to position (DMTP) task were examined. The percentage of correct choices (choice accuracy), number of trials completed and intertrial intervals were measured. Discriminability and response bias were also calculated, using signal detection analysis. Scopolamine HBr (0.1 mg/kg), but not scopolamine MeBr (0.1 mg/kg), significantly and consistently reduced the choice accuracy and discriminability, but neither affected the other measurements. E2020 (0.03-1.0 mg/kg) had no effect on the baseline performance in the DMTP task, but at 1.0 mg/kg, it significantly attenuated the deficits in choice accuracy induced by scopolamine. 4-AP (0.001-0.1 mg/kg) had no effect on either baseline performance or deficits induced by scopolamine. Apamin (0.1-0.4 mg/kg) had no effect on choice accuracy and discriminability. Apamin also failed to attenuate the scopolamine-induced deficits. When administered in combination with scopolamine, apamin at 0.4 mg/kg significantly decreased the number of trials completed and increased the intertrial interval relative to that of the control group. Taken together, these results demonstrate that K+ channel blockers (4-AP and apamin), unlike a cholinesterase inhibitor (E2020), fail to reverse the scopolamine-induced deficits in the DMTP task.
 ...
PMID:Effects of the potassium channel blockers, apamin and 4-aminopyridine, on scopolamine-induced deficits in the delayed matching to position task in rats: a comparison with the cholinesterase inhibitor E2020. 949 27

Alzheimer's disease is the most frequent form of dementia, where behavioral and cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported by caregivers. Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer's disease. Cognitive impairment was equally distributed among the subjects. Patients, aged 68 to 76 years old, were randomized to receive inhibitors of cholinesterase (Donepezil, 5 mg/day) alone, or inhibitors of cholinesterase plus selective serotonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We followed up all the patients for one year, with particular concern for neuropsychological aspects associated with eventual behavioral changes. Results indicate that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients and caregivers. Side effects in both groups were few, and there were no study withdrawals. This paper discusses the relationship between dementia and depression, and presents our finding that depressive symptoms, if specifically treated, tend to reduce caregiver stress and improve well-being in patients with Alzheimer's disease.
 ...
PMID:Depression and Alzheimer's disease: symptom or comorbidity? 1250 80

A series of difunctionalized 4-hydroxybenzaldehyde derivatives were designed, synthesized and evaluated as cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)) inhibitors. The results demonstrated that all the compounds had more potent AChE and BChE inhibitory activities than galanthamine-HBr, one of the best cholinesterase inhibitors known so far. The inhibition mechanism revealed that the best active compound 4e displayed a mix-type mode of AChE and BChE by its dual-site interactions with the catalytic triad active center and the peripheral anionic site (PAS) of enzyme. All these data suggested that further development of such compounds may be of interest.
 ...
PMID:Design, synthesis and evaluation of difunctionalized 4-hydroxybenzaldehyde derivatives as novel cholinesterase inhibitors. 2082 2