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 main thrust of the meeting was, as always, basic research in behavioral neuroscience defined in a broad sense. Learning and memory, feeding and drinking, reward mechanisms, development of the CNS, anxiety and stress were the main topics covered. In a public lecture associated with the meeting, Larry Reid (Rensselaer Polytechnic Institute, Troy, NY, USA) reviewed the quite compelling evidence in favor of the effectiveness of naltrexone for preventing relapse in former alcoholics. He also presented preclinical data demonstrating the remarkable effects of naltrexone given together with isradipine (Novartis AG) in blocking the rewarding effects of cocaethylene. This combination of drugs could thereby constitute a treatment for alcoholism complicated by cocaine abuse. Of potential therapeutic interest was also the description of the preclinical pharmacology and a phase II trial of a new cholinesterase inhibitor, methanesulfonyl fluoride (University of Texas). The possible physiological functions of sigma opioid receptors and the pharmacological properties of sigma receptor ligands were discussed at one of the symposia. Among the subjects covered were the potential use of sigma1 antagonists in the treatment of cocaine addiction and the efficiency of sigma1 agonists for preventing the decline in cognitive functions associated with old age.
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PMID:International Behavioral Neuroscience Society - ninth annual meeting. 1608 41

Donepezil is a potent acetylcholinesterase inhibitor that also interacts with the sigma1 receptor, an intracellular neuromodulatory protein. In the present study, we analyzed the antiamnesic and neuroprotective activities of donepezil in a mouse hypoxia model induced by repetitive CO exposure, comparing donepezil's pharmacological profile with other cholinesterase inhibitors tacrine, rivastigmine, and galanthamine, and the reference sigma1 agonist igmesine. CO exposure induced, after 7 days, hippocampal neurodegeneration, analyzed by Cresyl violet staining, and behavioral alterations, measured using spontaneous alternation and passive avoidance responses. When injected 20 min before the behavioral tests, i.e., 7 to 8 days after CO, all drugs showed antiamnesic properties. Preadministration of the sigma1 receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047) blocked only the igmesine and donepezil effects. The neuroprotective activity of the drugs was tested by injection 20 min before the first CO exposure (preinsult protection) or by injection 1 h after the last CO exposure (postinsult protection). All drugs alleviated the hypoxia-induced neurodegeneration and behavioral impairments when injected before CO exposure. Preadministration of BD1047 blocked both the igmesine and donepezil effects. However, when injected after CO exposure, only igmesine and donepezil induced effective neuroprotection, and the morphological and behavioral effects were BD1047-sensitive. These results showed that donepezil is a potent antiamnesic and neuroprotective compound against the neurodegeneration induced by excitotoxic insult, and its pharmacological actions as both an acetylcholinesterase inhibitor and sigma1 receptor agonist contribute to its marked efficacy. In particular, the drug is a more potent postinsult protecting agent compared with more selective cholinesterase inhibitors.
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PMID:Antiamnesic and neuroprotective effects of donepezil against learning impairments induced in mice by exposure to carbon monoxide gas. 1655 35