Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors
| Autor: | Carol C. Edwards, Lyudmila Tsurkan, Janice L. Hyatt, Philip M. Potter, M. Jason Hatfield |
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| Rok vydání: | 2013 |
| Předmět: |
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Molecular Drug Aché Physostigmine media_common.quotation_subject Phenylcarbamates Rivastigmine Pharmacology Toxicology Article Carboxylesterase law.invention chemistry.chemical_compound law Detoxification medicine Humans Drug Interactions Cholinesterase media_common biology Chemistry General Medicine Recombinant Proteins language.human_language Intestines Kinetics Liver Biochemistry biology.protein Recombinant DNA language Cholinesterase Inhibitors Xenobiotic Carboxylic Ester Hydrolases medicine.drug |
| Zdroj: | Chemico-Biological Interactions. 203:226-230 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2012.10.018 |
| Popis: | Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms, We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer’s disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. |
| Databáze: | OpenAIRE |
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